Role of vitamins in the development and treatment of osteoporosis (Review)

Jiang,Mingze; Li,Genghan; Yang,Keda; Tao,Lin

doi:10.3892/ijmm.2025.5550

Role of vitamins in the development and treatment of osteoporosis (Review)

Authors:
- Mingze Jiang
- Genghan Li
- Keda Yang
- Lin Tao
View Affiliations

Affiliations: Department of Orthopedics, First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China, First Department of Clinical Medicine, China Medical University, Shenyang, Liaoning 110001, P.R. China
Published online on: May 12, 2025 https://doi.org/10.3892/ijmm.2025.5550
Article Number: 109
Copyright: © Jiang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Osteoporosis has escalated into a pressing public health challenge amidst global demographic aging. Conventional diagnostic approaches and therapeutic interventions demonstrate growing limitations in both risk stratification and epidemiological control. In this context, serological monitoring and targeted nutrient supplementation emerge as promising preventive strategies. Vitamins, fundamental regulators of cellular homeostasis, demonstrate particular significance in bone remodeling processes. The present comprehensive review elucidates the pathophysiological mechanisms through which specific vitamins differentially modulate osteoblastic activity and osteoclastic regulation, summarizing contemporary evidence from the molecular to clinical research levels. While vitamin A exhibits dual effects, other vitamins predominantly show positive impacts on bone homeostasis. Oxidative stress and inflammation are key pathological changes associated with osteoporosis. Vitamins play a protective role by enhancing the expression of antioxidant enzymes, activating antioxidant pathways and inhibiting the secretion of inflammatory cytokines, thereby mitigating these conditions. Serum vitamin concentrations exhibit significant correlations with bone mineral density alterations and osteoporosis progression, providing predictive biomarkers for fracture risk assessment. However, serum vitamin profiles exhibit marked heterogeneity across osteoporosis risk strata, necessitating population‑specific therapeutic protocols. Precision‑adjusted supplementation strategies effectively attenuate pathological bone resorption while preserving physiological remodeling homeostasis. The present review systematically delineates the therapeutic potential of vitamins in osteoporotic management, underscoring the necessity for evidence‑based precision nutrient protocols tailored to at‑risk populations to prevent disease progression.

Introduction

Osteoporosis is a progressive metabolic bone disorder defined by diminished bone mineral density (BMD) and microarchitectural deterioration of osseous tissue (1). A previous report indicated that the prevalence of osteoporosis among middle-aged and elderly individuals in China is ~33.49%, broken down as 20.73% in men and 38.05% in women (2). Osteoporosis primarily manifests as pain and skeletal deformities, with fractures constituting the most severe complication that imposes substantial burdens on patients and significantly compromises their quality of life (3). Osteoporotic fractures predominantly comprise vertebral compression fractures and hip fragility fractures. Notably, hip fractures represent >40% of these cases, while the refracture rate following vertebroplasty for vertebral compression fractures approaches 20% (4,5). Skeletal homeostasis is dynamically regulated through coupled bone remodeling processes, mediated by osteoblastic bone formation and osteoclastic bone resorption within specialized bone multicellular units (6). The balanced interplay between osteoblastic and osteoclastic activities maintains physiological bone turnover while preventing pathological alterations in bone mass. However, age-related endocrine changes, particularly estrogen deficiency in postmenopausal women, coupled with metabolic dysregulation such as chronic hyperglycemia and adiposity, disrupt this equilibrium. This imbalance leads to predominant osteoclastic resorption over osteoblastic formation, resulting in progressive bone mass depletion and eventual osteoporotic deterioration (7). Owing to the exclusion of BMD assessments from routine physical examinations and insufficient awareness of bone health maintenance, patients frequently present with clinically detectable reductions in BMD only upon the manifestation of severe complications. Consequently, implementing proactive diagnostic measures and preventative strategies becomes imperative for populations with elevated osteopathic risks.

Vitamins represent a category of essential micronutrients that must be acquired through dietary sources to support fundamental physiological processes. These micronutrients serve critical functions in human growth, metabolic regulation and developmental processes (8,9). Although vitamins neither constitute structural components of bodily tissues nor serve as energy substrates, they mediate the regulation of biochemical metabolism through enzymatic cofactor activities (10). Vitamins play crucial roles in maintaining skeletal integrity and facilitating bone repair mechanisms (11). Clinical evidence demonstrates that vitamin deficiencies constitute significant risk factors for osteoporosis development (12). Vitamin D plays a pivotal role in skeletal mineralization through the regulation of calcium homeostasis; it facilitates intestinal calcium absorption by inducing the expression of calcium-binding proteins and enhancing the bioavailability of calcium salts within the gastrointestinal tract (13). Clinical evidence also supports the therapeutic efficacy of vitamin B supplementation in enhancing BMD (14). Additionally, vitamins C and E demonstrate therapeutic potential in ameliorating oxidative stress-mediated skeletal deterioration, effectively mitigating osteoporotic bone loss in clinical populations (15). Furthermore, Vitamin K has been established as a critical biochemical indicator for assessing osteoporotic vertebral fracture risk (16). This evidence collectively establishes that vitamins play integral roles in the diagnostic evaluation, preventive strategies and therapeutic management of osteoporosis. The present review systematically examines the regulatory functions of vitamins in bone metabolism while elucidating the pathophysiological mechanisms underlying osteoporosis associated with vitamin homeostasis dysregulation.

Vitamins and osteoporosis

Vitamin A plays a critical role in regulating cellular differentiation and metabolic homeostasis, and is predominantly stored in hepatic tissues of animal-derived food sources (17). Vitamin A and its provitamin precursors exhibit osteoprotective effects by stimulating osteoblastic activity while suppressing osteoclastic differentiation through retinoic acid receptor-mediated transcriptional regulation (18). Vitamin A exerts a dose-dependent influence on bone metabolism, where moderate short-term intake enhances bone formation, while chronic excessive accumulation demonstrates catabolic effects on skeletal integrity (19). Recent investigation has revealed stage-dependent effects of vitamin A during osteogenesis, promoting osteoblast differentiation while impairing matrix mineralization (18). Retinoid receptors participate in the modulatory effects of vitamin A in bone metabolism (16). Vitamin A deficiency induces significant developmental abnormalities characterized by impaired skeletal morphogenesis and aberrant cortical bone remodeling (20). Lind et al (21) demonstrated that supraphysiological vitamin A intake induces aberrant vascular endothelial growth factor overexpression, thereby compromising bone marrow microvascular integrity and predisposing to spontaneous fracture development (21). Emerging evidence suggests that vitamin A demonstrates therapeutic potential in ameliorating mechanical loading-induced skeletal dysregulation (22). Retinol and retinoic acid represent the principal bioactive forms of vitamin A. A significant U-shaped relationship exists between plasma retinol concentrations and BMD (23). Moderate enhancement of retinol signaling promotes osteogenesis while inhibiting osteoclast genesis (24). Crosstalk exists between the Wnt/β-catenin signaling pathway and retinoic acid signaling pathways (25). In postmenopausal women, elevated serum retinol levels exhibit significant associations with accelerated bone loss and heightened risk of osteoporotic fractures (26). Excessive vitamin A leads to accumulation of its metabolite retinoic acid, which accelerates receptor activator of nuclear factor κB ligand (RANKL)-dependent osteoclast differentiation and subsequent bone mass reduction (27,28) (Table I). In animal experiments, retinoic acid was found to markedly decrease bone calcium and phosphorus by promoting bone resorption and collagen metabolism (29,30). All-trans retinoic acid further inhibits osteogenic activity through suppression of the canonical Wnt/β-catenin signaling pathways (31). Carotenes demonstrate beneficial effects on bone formation. Epidemiological studies have established that increased β-carotene intake enhances BMD and reduces the risk of fractures (32,33). The B vitamin complex exerts essential regulatory functions in skeletal metabolic homeostasis (34). Osteoporosis and hip fracture incidence have both been associated with inadequate dietary intake of B vitamins (35). Current research on the role of vitamin B1 in osteoporosis pathogenesis remains limited. Functioning as a coenzyme, vitamin B1 facilitates glycolytic metabolism in bone cells. Osteoblasts primarily rely on aerobic glycolysis for energy production, whereas osteoclasts predominantly utilize oxidative phosphorylation as their main energy-generating pathway (36). Vitamin B1 modulates osteoblastic glucose metabolism to regulate osteogenic processes. Preliminary evidence suggests its potential to inhibit RANKL-induced osteoclast differentiation, thereby mitigating osteoporosis progression (37). Vitamin B2 exerts beneficial effects on bone homeostasis. A clinical investigation has demonstrated that dietary vitamin B2 supplementation correlates with reduced osteoporosis incidence (38). Vitamin B2 promotes osteogenic differentiation and vascular angiogenesis, thereby enhancing bone mass accrual (39). Vitamin B2 treatment significantly upregulates the expression levels of Runt-related transcription factor 2 (Runx2) and β-catenin (40). Elevated vitamin B6 intake is associated with increased BMD at the hip and spine (41), while diminished serum vitamin B6 concentrations demonstrate a significant association with an elevated risk (42). Bioactivated vitamin B6 enhances in vivo osteointegration processes (43), while vitamin B6 deficiency impedes fracture repair by impairing callus maturation (44). Vitamin B9 supplementation demonstrates beneficial effects on BMD (14). Vitamin B9 enhances osteogenic differentiation by inducing the expression of Runx2 and alkaline phosphatase (ALP) (45). Vitamin B9 activates the canonical Wnt/β-catenin signaling pathway during osteogenic differentiation (46) (Table I). Adults with suboptimal vitamin B12 status exhibit compromised skeletal integrity and diminished bone health outcomes (47). Vitamin B12 deficiency is associated with diminished total skeletal mass and elevated fracture susceptibility (48,49). Additionally, deficiency of the vitamin B family leads to high homocysteine concentrations, which could promote bone resorption and increase the fracture risk (50). Hyperhomocysteinemia potentiates osteoclastogenesis through enhanced catalytic activity of tartrate-resistant acid phosphatase (TRAP) and cathepsin K (CTSK) (51). Homocysteine exerts inhibitory effects on osteoblastic proliferation and mineralization, thereby compromising bone formation processes (52).

Table I

Role of vitamins in bone metabolism.

Table I

Role of vitamins in bone metabolism.

Vitamins	Mechanism	Effect in bone metabolism	(Refs.)
Vitamin A	Moderate: Promoting osteogenesis and inhibiting osteoclastogenesis via the Wnt/β-catenin pathway Excessive: Inhibiting Wnt signaling and promoting RANKL-mediated osteoclast differentiation	Osteoblast (+) Osteoclast (−) Osteoblast (−) Osteoclast (+)	(25,26,28, 29)
Vitamin B1	Inhibiting RANKL-induced osteoclast differentiation	Osteoclast (−)	(38)
Vitamin B2	Increasing the expression of Runx2 and β-catenin	Osteoblast (+)	(41)
Vitamin B6	Contributing to osteointegration and promoting callus maturation	Osteoblast (+)	(44,45)
Vitamin B9	Inducing the expression of Runx2 and ALP Activating the Wnt/β-catenin signaling pathway	Osteoblast (+)	(46,48)
Vitamin C	Increasing the expression of BMP2, Runx2, osteocalcin and Collagen I Participating in the formation of calcified nodules	Osteoblast (+)	(61,62,65)
Vitamin C	Decreasing the concentration of CTX-1 and RANKL Inhibiting the expression of TRAP and CTSK	Osteoclast (−)
Vitamin D	Assisting Ca²⁺ in passing through the osteoblast membrane Increasing the expression of SMAD1-3 and 5, and β-catenin Increasing the expression of Runx2 and Collagen I Increase ALP activity and osteocalcin expression	Osteoblast (+)	(69-71,73)
Vitamin E	Increasing the expression of cyclin D1 and c-myc, and activating the Wnt/β-catenin signaling pathway in osteoblasts Increasing the expression of BMP2, osterix, collagen I and osteocalcin Reducing the production of serum C-terminal telopeptide of type I collagen Deactivating RANKL-mediated osteoclast differentiation	Osteoblast (+) Osteoclast (−)	(83-85,89,90)
Vitamin K1	Participating in the biosynthesis of osteocalcin and bone matrix Gla protein	Osteoblast (+)	(96)
Vitamin K2	Increasing the expression of Runx2 and osteocalcin via the Bcl-6/STAT axis and the IL-6/JAK/STAT signaling pathway	Osteoblast (+)	(100)

[i] (+), positive effects; (−), negative effects; RANKL, receptor activator of nuclear factor κB ligand; Runx2, runt-related transcription factor 2; ALP, alkaline phosphatase; CTX-1, C-terminal peptide of type I collagen; TRAP, tartrate-resistant acid phosphatase; CTSK, cathepsin K.

Vitamin C, scientifically termed ascorbic acid, critically catalyzes collagen biosynthesis within osseous matrices (53). Vitamin C in combination with β-glycerophosphate and dexamethasone constitutes a standard osteogenic differentiation induction protocol (54). Clinical investigations have established a positive correlation between serum vitamin C concentrations and BMD, with enhanced dietary vitamin C intake demonstrating favorable associations with improved bone mass parameters (55). Increased vitamin C intake is associated with elevated BMD at the hip and lumbar spine (56), and a diet high in vitamin C demonstrates a significant reduction in hip fracture risk (57). Vitamin C actively contributes to the regenerative processes following osseous defect formation (58). Vitamin C and its derivatives demonstrate significant osteogenic enhancement (59). Vitamin C administration upregulates the expression of BMP2, Runx2, Osteocalcin and Collagen I during osteogenic differentiation processes (60). Vitamin C also facilitates proline hydroxylase activity to catalyze collagen biosynthesis and post-translational maturation, thereby supporting osteocalcin production and coordinating bone tissue remodeling processes (61). Vitamin C metabolism is mechanistically linked to the biosynthesis of procollagen type I N-terminal propeptide (PINP) (62). Additionally, vitamin C facilitates calcified nodule formation during biomineralization and activates extracellular matrix deposition processes (63). Vitamin C downregulates the expression of TRAP and CTSK, effectively inhibiting osteoclast differentiation (60) (Table I).

Vitamin D serves as a critical biomarker for bone formation, and its deficiency directly contributes to osteoporosis development (64). Vitamin D is closely related to bone metabolism and its main function is to regulate the absorption of calcium and phosphorus, which are involved in neo-osteogenesis (65). Vitamin D primarily enhances bone tissue calcification by regulating plasma calcium and phosphorus levels, and promoting their deposition as bone salts (66); it facilitates Ca2+ transport across osteoblast membranes into osseous tissue (67). Vitamin D further stimulates osteogenic signaling pathways through upregulation of SMAD1-3 and 5 and β-catenin expression (68). Vitamin D stimulation significantly upregulates the expression of osteogenic biomarkers, including Runx2 and collagen type I (69). The vitamin D receptor (VDR) critically regulates skeletal metabolic homeostasis (70). VDR activation enhances ALP enzymatic activity and stimulates osteocalcin biosynthesis in osteoblasts (71) (Table I). Vitamin D further induces VDR activation within osteoblasts, demonstrating the capacity to suppress osteoclastic activity (72). VDR-targeted genetic interventions demonstrate therapeutic efficacy in bone metabolic regulation, establishing innovative pharmacological strategies for osteoporosis management (73). Additionally, Vitamin D exerts dual therapeutic effects by restoring trabecular microarchitecture and augmenting musculoskeletal function, thereby enhancing skeletal integrity and physical performance in osteoporotic populations (74). Vitamin D, as a fundamental supplement for skeletal health, is extensively employed in osteoporosis clinical management alongside calcium. A longitudinal investigation involving over 20,000 participants demonstrated that sustained bolus vitamin D administration maintained fracture risk neutrality, affirming its safety in both preventive and therapeutic osteoporosis applications (75). Moreover, vitamin D deficiency serves as a principal etiological determinant in the pathogenesis of pediatric rickets (76). Vitamin D deficiency precipitates dysregulated calcium-phosphorus homeostasis and impairs both metaphyseal mineralization and skeletal matrix maturation. Enhanced vitamin D supplementation during pregnancy and the neonatal period effectively prevents the development of rickets (77).

Vitamin E and its derivatives demonstrate beneficial effects on bone metabolism (78). Vitamin E participates in the maintenance of bone homeostasis by modulating osteocyte-derived bone-related peptides (79) Diminished serum concentrations predispose to the development of hip fractures (80). Vitamin E stimulates osteoblast proliferation through upregulation of cyclin D1 and c-myc expression, while concurrently enhancing osteogenic differentiation via activation of the canonical Wnt/β-catenin signaling pathway (81). Osteogenic markers, including BMP-2, Osterix, Collagen type I and Osteocalcin, are upregulated to induce osteogenesis (82,83). Vitamin E preserves plasma membrane integrity in osteocytes subjected to mechanical loading by mitigating membrane disruptions (84). Vitamin E exhibits protective effects on mineralized surfaces, effectively preventing bone erosion (85). Meanwhile, it also significantly suppresses osteoclast-specific biomarker expression and attenuates osteoclastic resorptive activity (86). Vitamin E reduces serum levels of type I collagen C-terminal telopeptide, thereby suppressing bone resorption activity (87). Vitamin E deficiency activates RANKL-mediated osteoclast genesis in multinucleated precursor cells (88) (Table I).

Vitamin K constitutes a critically underrecognized modulator of skeletal homeostasis (89). Genetic polymorphisms in vitamin K regulatory enzymes constitute significant genetic determinants for osteoporosis risk stratification (90). Vitamin K deficiency significantly accelerates bone loss progression (91). Increased vitamin K intake reduces osteoporosis risk and prevents fractures (92). Both osteocalcin and matrix Gla protein (MGP) are vitamin K-dependent proteins (93). Vitamin K1 is essential for the biosynthesis of osteocalcin and MGP (94). Periostin, Protein S and growth arrest-specific 6 protein constitute vitamin K1-dependent proteins essential for skeletal homeostasis (95). Vitamin K2 demonstrates beneficial regulatory effects on skeletal homeostasis through dual mechanisms of stimulating osteoblastic activity and suppressing osteoclastic differentiation (96). Vitamin K2 has been applied as a supplement for the prevention and treatment of osteoporosis (97). Transcriptomic profiling demonstrated vitamin K2-mediated upregulation of Runx2 and osteocalcin through coordinated activation of the Bcl-6/STAT transcriptional axis and the IL-6/JAK/STAT signaling cascade (98) (Table I). The intestinal microbiota and metabolites regulate bone metabolism (99). Integrative analysis of 16S rRNA sequencing data with serum bone metabolic parameters revealed Bacteroides-mediated modulation of vitamin K2 homeostasis and skeletal remodeling processes (100). Vitamin K2 enhances osteogenic differentiation and matrix mineralization through autophagy pathway activation in osteoblasts (101). Vitamin K in combination with vitamin D and calcium may constitute a more efficacious supplement regimen for osteoporosis prophylaxis and therapeutic management (102,103). However, notably, vitamin K antagonist oral antibiotics demonstrate diminished BMD and elevated fracture susceptibility through coherent pharmacological mechanisms (104).

Vitamins in high-risk populations for osteoporosis

Postmenopausal women

Vitamins, as essential micronutrients, demonstrate significant associations with osteopenia in postmenopausal women (105). Reduced vitamin intake exacerbates postmenopausal osteoporotic deterioration (106). Vitamin A serves as a critical supplement for postmenopausal women, effectively enhancing health-related quality of life (107). Serum carotenoid concentrations demonstrate significant associations with estrogen receptor-positive malignancy risk (108). However, elevated circulating vitamin A concentrations constitute a significant risk factor for osteoporosis (26). Chronic supplementation significantly elevates fracture incidence (109). Vitamin B9 and vitamin B12 are the primary B vitamins associated with bone metabolism in postmenopausal women. Epidemiological evidence indicates that vitamin B9 and B12 deficiencies are associated with an increased incidence of asymptomatic osteoporotic vertebral fractures (110). Vitamin B9 demonstrates beneficial regulatory effects through upregulation of osteocalcin biosynthesis and β-cross-linked C-telopeptide expression (111). Vitamin B12 serves as a protective factor against osteoporosis in postmenopausal women (112). Vitamin C stimulates gonadal secretory activity and enhances circulating estrogen levels (113); it primarily mediates the enhancement of endothelial function in postmenopausal physiological states (114,115). Serum vitamin C concentrations demonstrated an inverse association with the pathogenesis of postmenopausal osteoporosis (116). Plasma vitamin C deficiency serves as a significant predictive biomarker for hip BMD (117). Vitamin C-enriched dietary regimens ameliorate the dysfunctional crosstalk among skeletal, muscular and adipose tissues secondary to estrogen deficiency through multi-tissue regulatory mechanisms (118). Vitamin D is essential for female reproductive physiology, with its receptor (VDR) mediating therapeutic benefits within the genitourinary system (119). Vitamin D deficiency is associated with premature menopause onset and diminished reproductive lifespan in women (120). Serum 25-hydroxyvitamin D [25(OH)D] levels are associated with the healthy index (lower levels of glycohemoglobin, glucose and higher levels of HDL) of postmenopausal women (121). Serum 25(OH D concentrations demonstrated significant correlations with health status indices in postmenopausal populations (122). Vitamin D is critical for maintaining BMD and reducing fracture risk in postmenopausal women (123), serving as a pivotal bone turnover marker that enhances bone quality and mechanical strength (124). Postmenopausal women with combined vitamin D insufficiency and elevated circulating retinol concentrations demonstrate significantly heightened susceptibility to osteoporotic progression (125). Serum vitamin D metabolites serve as critical diagnostic biomarkers for predicting the onset of postmenopausal osteoporosis (126). Therapeutically, vitamin D supplementation is employed to prevent estrogen deficiency-induced bone loss (127). Vitamin D combined with calcium supplementation is more effective for improving the process of bone remodeling (128). Vitamin D upregulates irisin expression to synergistically augment musculoskeletal function and BMD (129). Vitamin E, scientifically termed tocopherol, demonstrates the capacity to stimulate estrogen biosynthesis and secretory processes (130). Vitamin E has been incorporated into hormone replacement regimens, serving as an adjuvant to mitigate climacteric symptomatology (131). Oral gavage of vitamin E significantly enhances bone mineral content and restores trabecular microarchitecture in ovariectomized (OVX) rat models (132). The principal therapeutic mechanism involves sclerostin downregulation, which enhances osteogenic activity through modulation of the RANKL/osteoprotegerin equilibrium (133). Meanwhile, vitamin E suppresses estrogen deficiency-driven monocyte/lymphocyte proliferation, thereby attenuating inflammation-mediated osteoclast differentiation (134). The antioxidative capacity of vitamin E attenuates oxidative stress-mediated bone resorption, thereby ameliorating osteopenic progression in postmenopausal women (135). Vitamin K demonstrates beneficial effects on bone ultrastructure enhancement (136); it plays a pivotal role in promoting osteogenic differentiation and facilitating matrix mineralization during postmenopausal bone remodeling. Oral vitamin K administration upregulates the expression of Runx2 and BMP2 while downregulating nuclear factor of activated T-cells cytoplasmic 1 (NFATC1) expression (137). Vitamin K derivatives also inhibited the expression of NFATc1 and CTSK to reverse bone resorption in a study with OVX mice (92). Vitamin K derivatives inhibited NFATc1 and CTSK expression, effectively reversing bone resorption in OVX mice (138). Vitamin K1 serves as a critical diagnostic and therapeutic biomarker for postmenopausal osteoporosis management (139). Elevated circulating vitamin K1 concentrations positively correlate with enhanced BMD in postmenopausal populations (140). Vitamin K2 supplementation may contribute to the maintenance and improvement of lumbar BMD by enhancing osteocalcin biosynthesis (141,142) (Table II). In summary, vitamins primarily counteract bone loss through direct interaction with estrogen receptors to modulate estrogen secretion or ameliorate pathological alterations induced by estrogen deficiency. Early assessment of serum vitamin levels facilitates the prevention of BMD reduction in postmenopausal women. Targeted vitamin supplementation further refines intervention strategies and enhances therapeutic outcomes for postmenopausal osteoporosis.

Table II

Vitamins in the development of postmenopausal osteoporosis.

Diabetic patients

Vitamins serve as critical factors in the synergistic regulation of blood glucose homeostasis. B-group vitamins function as coenzymes in glucose metabolism pathways, with vitamin B1 deficiency specifically impairing glucose oxidation, thereby inducing pyruvate accumulation and compromising cellular energy supply (143). Notably, vitamin B1 insufficiency is highly prevalent in diabetic populations (144). Serum vitamin B1 concentrations demonstrate a significant positive correlation with diabetes mellitus progression (145). Vitamin B1 supplementation demonstrates therapeutic efficacy in ameliorating osteoporosis associated with diabetes mellitus (146). Vitamin B12 deficiency is prevalent among diabetic patients, particularly following metformin administration (147). Vitamin B12 supplementation may mitigate the risk of hyperglycemia-associated fragility fractures (148). Vitamin C exerts indirect regulatory effects on blood glucose homeostasis. Notably, vitamin C has been shown to inhibit the formation of advanced glycation end products (149). Conversely, vitamin C has been demonstrated to promote insulin secretion, enhance the degree to which insulin promotes glucose breakdown and attenuate insulin resistance (150). Low serum vitamin C levels have been established as a significant contributing factor to reduced BMD in diabetic patients (55). Vitamin D plays a pivotal role in blood glucose homeostasis and the modulation of glycemic indicators (151). Serum 25(OH)D3 concentrations exhibit a progressive decline associated with diabetes mellitus progression (152). Vitamin D deficiency has been mechanistically linked to insulin resistance, potentiating the risk of diabetic osteoporosis through impaired bone metabolic efficiency (153). VDR activation has been shown to mitigate Wnt signaling pathway suppression and stimulate the upregulation of osteogenic marker proteins, thereby counteracting diabetes-associated bone resorption (154). Vitamin D-induced osteogenic effects on osteoblasts are mediated through forkhead box protein O1 (FoxO1) signaling inhibition (155,156). Vitamin E demonstrates therapeutic potential in modulating glycemic regulation (78). Vitamin E supplementation enhances glucose homeostasis through improved glucose-insulin regulatory mechanisms, while ameliorating hyperglycemia-associated bone resorption by upregulating PINP synthesis to stimulate osteogenic activity (157) (Fig. 1). Vitamin K2 upregulates SIRT1 expression to inhibit hyperglycemia-induced mesenchymal stem cell (MSC) ferroptosis (158). The synergistic administration of vitamins K2 and D3 represents a promising therapeutic strategy for the management of diabetic osteoporosis (159). In conclusion, vitamins primarily ameliorate bone loss in diabetic populations through their involvement in glucose metabolism and modulation of insulin secretory dynamics and bioactivity. Optimal-dose vitamin supplementation demonstrates dual efficacy in maintaining glycemic stability and attenuating hyperglycemia-driven osteoclastic resorption.

Figure 1

Positive effects of vitamins in diabetic osteoporosis. TCA, tricarboxylic acid cycle; VDR, vitamin D receptor; LRP, LDL receptor-related protein; GSK-3β, glycogen synthase kinase 3β; CKIα, casein kinase Iα; APC, adenomatous polyposis coli; TCF/LEF, T cell factor/lymphoid enhancer binding factor.

Obese groups

In obese populations, vitamin A deficiency exhibits a stronger association with pathological bone deterioration and microarchitectural degradation (18). Obesity demonstrates a significant inverse association with serum retinol concentrations (160). Vitamin A enhances lipid oxidative metabolism and promotes adipose tissue catabolism (161). Retinol-binding protein 4 serves as a critical adipokine mediating the regulatory effects of vitamin A on lipid metabolism, while exhibiting an inverse correlation with serum osteocalcin concentrations (162,163). The vitamin B group plays integral roles in lipid metabolic processes. Specifically, vitamin B2 orchestrates adipose tissue biosynthesis, catabolism and secretory regulation. Vitamin B2-enriched dietary regimens effectively reduce adipose accumulation while preventing BMD loss (157). Vitamin B9 activates the AMPK signaling pathway to attenuate high fat diet (HFD)-induced osteoporosis by increasing the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and antioxidant enzymes (164). Meanwhile, serum vitamin B12 concentrations exhibited a significant inverse association with adiposity indices (165). Vitamin C demonstrates inhibitory effects on triglyceride deposition and adipose tissue hypertrophy (166), and modulates MSC differentiation trajectories, preferentially steering lineage commitment toward osteogenesis while suppressing adipogenic propensity (167). Clinical investigations have established that dietary vitamin C sufficiency exerts preventive effects against the development of obesity-related osteoporosis (118). Comparative analysis stratified by body mass index revealed that obese individuals demonstrated a significant reduction in serum 25-hydroxyvitamin D concentrations relative to non-obese controls (168). Obese individuals exhibit impaired vitamin D metabolism that adversely impacts bone formation (169). In the osteoporotic population, serum 25(OH D3 levels (the predominant circulating form of vitamin D) demonstrate a significant inverse association with triglyceride concentrations, while exhibiting positive correlations with apolipoprotein A1, lipoprotein (a) and high-density lipoprotein cholesterol levels (170). Vitamin E inhibits the synthesis of cholesterol to treat hyperlipidemia (171). Vitamin E exerts inhibitory effects on hepatic cholesterol biosynthesis, thereby ameliorating hyperlipidemic conditions through modulation of key lipid metabolic pathways (172). Vitamin K demonstrates regulatory effects on adipose tissue metabolism (173). The supplementation of vitamin K in HFD rats was shown to prevent bone loss through dual mechanisms, namely, enhancing osteocalcin-mediated bone formation and suppressing RANKL-induced osteoclastic resorption (174). The combined administration of vitamin K2 and D3 synergistically enhanced the expression of osteogenic transcription factors, specifically osteocalcin, osterix and Runx2, in diet-induced obese murine models (159) (Table III). Overall, vitamins serve as key regulatory factors in lipid metabolism homeostasis. Adequate vitamin intake prevents adipocyte hypertrophy by optimizing lipid turnover rates and attenuating hyperlipidemia-associated comorbidities. Implementation of a vitamin-enriched dietary regimen synergized with structured physical activity constitutes an evidence-based intervention for improving metabolic parameters and preserving BMD in obese populations.

Table III

Vitamins in the development of obesity-associated osteoporosis.

Modulatory mechanism of vitamins in osteoporosis

Antioxidant effect

Oxidative stress has been identified as a pathophysiological hallmark in clinically vulnerable cohorts predisposed to osteoporosis, functioning as a critical underlying mechanism driving accelerated BMD decline (7). Vitamins A, C and E are primary regulators of the redox balance. Vitamin A elevates thioredoxin reductase expression to counteract nitric oxide-induced oxidative damage and augments glutathione peroxidase activity to reduce free radical accumulation (175). Meanwhile, vitamin A effectively attenuates lipid peroxidation chain reactions and suppresses malondialdehyde production in lipid metabolic processes (176). Vitamin A intake enhances systemic antioxidant capacity through dual pathways: Attenuating plasma sulfhydryl (SH) group depletion while mitigating oxidative protein modifications (177). Vitamin C exerts antioxidant effects through two primary mechanisms: Protecting SH groups from oxidation, and serving as an electron donor to regenerate reduced glutathione (GSH) from its oxidized form (GSSG) (178). Vitamin E suppresses lipid peroxidation chain reactions, thereby attenuating oxidative stress-induced cellular damage. Concurrently, it facilitates the transfer of membrane-bound lipid peroxides to vitamin C for subsequent enzymatic reduction into non-toxic fatty acids and glycerol derivatives (15,179). Vitamin E significantly enhances systemic antioxidant defense by elevating total antioxidant capacity in serum through potentiation of radical-scavenging enzymatic systems (180).

Antioxidant vitamins demonstrate significant therapeutic potential in enhancing BMD through attenuation of oxidative stress-mediated bone resorption and promotion of osteoblastic activity (181). Epidemiological evidence substantiates that dietary vitamins A, C and E confer significant risk reduction for osteoporosis through synergistic mitigation of oxidative stress, while serving as essential modulators of bone remodeling homeostasis (182). The composite dietary antioxidant index, encompassing vitamins A, C and E, demonstrates a significant inverse correlation with BMD during osteoporotic progression (106). Oral antioxidant vitamins demonstrate therapeutic benefits in attenuating age-related physiological decline and ameliorating oxidative stress-associated bone deterioration through comprehensive modulation of redox homeostasis (183). Meanwhile, these antioxidant vitamins, especially vitamin E, can notably decrease fracture occurrence at any site (184). Vitamins C and E enhance collagen synthesis, osteogenic differentiation and matrix mineralization through their antioxidant properties (185). Vitamin C demonstrates therapeutic efficacy in counteracting oxidative skeletal damage resulting from diverse pathological stressors (186,187). Vitamin C treatment effectively reduces stress-induced osteoblast death and inhibits RANKL/macrophage colony-stimulating factor-mediated osteoclast differentiation under oxidative conditions (188). Sodium-dependent vitamin C co-transporters orchestrate the homeostatic regulation of redox balance in osseous tissue through dual mechanisms: Modulating transcriptional activation of antioxidant enzyme systems, while coordinating osteogenic differentiation processes (189,190). Vitamin E exerts bone-protective effects during osseous metabolism through its antioxidant properties, which mitigate oxidative damage to bone tissue components and maintain redox homeostasis (191). Vitamin E modulates the redox balance to suppress adipogenic differentiation in bone marrow MSCs, thereby preserving their osteogenic potential under oxidative conditions (192). Vitamin E protects osteoblasts from reactive oxygen species (ROS)-induced oxidative stress by elevating the GSH redox ratio (GSSH/GSSG), thereby enhancing cellular antioxidant defenses in bone-forming cells (193). Moreover, vitamin E restores mitochondrial function to suppress ROS-mediated osteoclastogenesis (86). Multiple vitamins modulate redox processes to regulate bone metabolic equilibrium. Activated vitamin D enhances mitochondrial ultrastructure and functional restoration, thereby optimizing redox homeostasis in osseous tissue (194). Vitamin D upregulates antioxidant enzyme expression to alleviate oxidative stress, thereby preventing osteoblast apoptosis through enhanced cellular redox homeostasis (195). VDR activation suppresses oxidative damage-induced osteoblast ferroptosis through Nrf2/glutathione peroxidase 4 pathway stimulation (196) (Fig. 2). Pantothenic acid orchestrates dual cytoprotective mechanisms through FoxO1/2 and Nrf2 signaling pathway activation, attenuating osteoclastogenesis via suppression of intracellular ROS overproduction (197). Vitamin K2 functions as an antioxidant in bone tissue engineering, effectively reducing ROS-induced damage to enhance bone repair processes (198). Vitamin K2 derivatives demonstrate inhibitory effects on oxidative stress-mediated osteoblast apoptosis (199).

Figure 2

Antioxidant effects of vitamins in the prevention and treatment of osteoporosis. GSH, glutathione; GSSG, oxidized glutathione; MDA, malondialdehyde; MSC, mesenchymal stem cell; ROS, reactive oxygen species; Nrf2, nuclear factor erythroid 2-related factor 2; GPX4, glutathione peroxidase 4; Tf, transferrin; SOD, superoxide dismutase.

Anti-inflammatory effect

Inflammation is an important pathogenic factor in the development of osteoporosis (200). Vitamin C demonstrates anti-inflammatory efficacy in OVX rats by attenuating TNF-α-mediated inflammatory infiltration in osseous tissues (201). Vitamin D deficiency induces systemic metabolic derangements and endocrine axis imbalance, culminating in elevated secretion of pro-inflammatory cytokines IL-6 and TNF-α (122). Vitamin D deficiency is also associated with an elevated erythrocyte sedimentation rate, C reactive protein (CRP) level and IL-6 level, which has a negative effect on BMD by decreasing osteocalcin (202). Vitamin D deficiency is associated with elevated levels of inflammatory markers (erythrocyte sedimentation rate (ESR), CRP and IL-6), which collectively contribute to reduced BMD via inhibition of osteocalcin production (203,204). Vitamin E supplementation attenuates inflammatory responses through downregulation of IL-1, IL-6 and CRP, effectively inhibiting osteoporotic progression (205). Vitamin K2 suppresses the secretion of pro-inflammatory cytokines, specifically IL-1α, IL-1β and TNF-α (206). Vitamin K2 suppresses both the activation and proliferation of circulating T cells, thereby enhancing bone mass through immunoregulatory mechanisms (207). Vitamin A exerts detrimental effects on bone metabolism through pro-inflammatory pathways. Specifically, retinoic acid suppresses the osteogenic differentiation of MSCs by stimulating the NF-κB/NLRP3 inflammasome axis and triggering IL-1β release (208). Downregulation of IL-6 secretion correlates with reduced expression of ALP and osteocalcin, critical biomarkers of osteogenic differentiation (209).

Discussion

Amidst the global demographic aging trend and the proliferation of sedentary lifestyle patterns, contemporary healthcare systems face escalating demands for enhanced quality-of-life metrics and optimized management of chronic degenerative diseases. Osteoporosis, a prevalent bone metabolic disorder, is pathologically manifested as progressive deterioration of bone microarchitecture with concomitant declines in mineral density (210). Current diagnostic paradigms rely on dual-energy X-ray absorptiometry (DXA) as the clinical gold standard, while suffering from inherent limitations, including cost-prohibitive screening protocols and suboptimal diagnostic accuracy in heterogeneous populations due to physiological confounding factors (211). Meanwhile, current osteoporosis treatment primarily employs drugs that directly stimulate osteogenesis and suppress osteoclastogenesis, yet these therapeutic approaches demonstrate constrained clinical efficacy and notable adverse effects (212). This context necessitates the development of novel diagnostic methodologies and therapeutic regimens to address contemporary clinical requirements in osteoporosis management.

Vitamins constitute indispensable micronutrients critical for human physiological homeostasis. These compounds orchestrate fundamental biological processes encompassing substrate metabolism, bioenergetic flux and homeostatic governance (213). Emerging evidence has elucidated their regulatory roles in bone metabolism through pleiotropic mechanisms (214,215). The present review systematically delineates vitamin-mediated physiological networks and elucidates their differential modulatory effects across heterogeneous bone tissue compartments. In the diagnostic paradigm, serum vitamin D quantification combined with bone turnover marker profiling augments the clinical utility of DXA through comprehensive evaluation of osteoporotic status (216). Research has also demonstrated the potential of other vitamins in the prediction of the risk of osteoporosis. Vitamin K and its derivatives have been confirmed to decrease in serum concentration earlier than vitamin D during the development of osteoporosis, suggesting that their measurement might detect the trend of bone loss earlier (126). Vitamin E demonstrates predictive value for BMD, although its clinical utility is confounded by demographic variables, including age, sex and ethnicity (217). Quantitative analysis of multiple vitamins in the blood is a potential method for predicting bone mass and evaluating bone mass based on different conditions. Vitamins are also effective substances for preventing and treating osteoporosis. In addition to the dual effects of vitamin A, other related vitamins showed positive effects on bone homeostasis. Vitamin D-calcium co-supplementation is recognized as the foundational therapeutic adjuvant in osteoporosis management (218). Moreover, the present review demonstrates that vitamins could increase the expression of osteogenic biomarkers and promote the mineralization of the bone matrix. Inhibition of bone resorption could also be enhanced after vitamin intake. Deeply exploring the role of vitamins in the development of osteoporosis contributes to optimizing diagnosis and treatment plans.

Vitamin disturbance is common in high-risk populations for osteoporosis. In postmenopausal women, vitamins participate in the regulation of reproductive function. Vitamins influence the secretion of estrogen, and estrogen performs biological functions through vitamin receptors. Vitamins are also important mediators involved in the action of estrogen in bone metabolism, and are associated with the development of osteoporosis. Vitamins A and D could also predict the risk of osteoporotic fractures in postmenopausal women. In diabetic patients, vitamin supplementation is beneficial for improving blood glucose and preventing complications. Vitamins not only regulate glucose metabolism processes, but also increase sensitivity and reduce resistance to insulin. Conventional treatments for diabetes, such as oral metformin, could lead to deficiencies in certain vitamins. Therefore, vitamins are essential in the maintenance and treatment of diabetes mellitus. In obesity groups, vitamins mainly affect blood lipid concentration by regulating the synthesis and decomposition of adipose tissue. On the one hand, vitamins induced osteogenic differentiation of MSCs rather than adipogenesis. On the other hand, reasonable lipid composition and content maintain the balance of bone formation and resorption. Additionally, the pathological changes can be improved with vitamin treatment in osteoporosis. Vitamins increase the expression of antioxidant enzymes and activate the antioxidant pathways to relieve the oxidative stress induced by the primary changes in osteoporosis. Decreasing the production of ROS and repairing the function of mitochondria contribute to attenuating osteoblast injury and inhibiting osteoclast activity. The redox balance is also positive for the maintenance of bone homeostasis. Improving the inflammatory response is another mechanism of vitamins in the treatment of osteoporosis. Vitamins inhibit the secretion of inflammatory cytokines and deactivate inflammasomes, which relieves the inhibition of osteogenesis. Circular RNA enrichment analysis has also indicated that vitamin digestion and absorption are associated with the development of osteoporosis (219,220). Based on large sample sizes of clinical trial data, it can be concluded that targeted delivery of vitamin molecules, such as loading nanoparticles, contributes to improving the diagnosis and treatment efficiency of osteoporosis in high-risk populations (221-223).

The present review systematically delineates the pleiotropic regulatory roles of vitamins in bone metabolism through their functional interplay with osseous homeostasis and skeletal remodeling dynamics. Blood vitamin content is significantly associated with the development of osteoporosis. The combination of multiple vitamins helps predict the risk of osteoporosis and bone loss under different primary etiologies. The positive effect of vitamins on bone formation determines the potential for osteoporosis treatment. The improvement of oxidative stress and inflammation in high-risk populations for osteoporosis also indicates the systemic modulation of vitamins. Specific vitamin supplements will effectively prevent and improve bone loss. Developing vitamin guidelines for people with osteoporosis is a research topic of considerable interest.

Availability of data and materials

Not applicable.

Authors' contributions

MJ was responsible for data curation, literature search methodology, use of the software for literature analysis and classification, and writing the original draft. GL was responsible for literature search methodology, validation of the literature and writing the original draft. KY was responsible for literature organization, use of the software for literature analysis, validation of the literature, and reviewing and editing the manuscript. LT was responsible for funding acquisition, project administration, and reviewing and editing the manuscript. All authors have read and approved the manuscript. Data authentication is not applicable.

Ethics approval and consent to participate

Not applicable.

Patient consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Abbreviations:

BMD	bone mineral density
VDR	vitamin D receptor
25(OH)D	25-hydroxyvitamin D
OVX	ovariectomized
HFD	high-fat diet
GSH	glutathione
MSC	mesenchymal stem cell
CRP	C reactive protein
ALP	alkaline phosphatase

Acknowledgments

Not applicable.

Funding

The present study was supported by project funding from the National Science Fund for Distinguished Young Scholars (grant no. 32200943), and Shenyang Young and Middle-Aged Innovative Talents Project (grant no. RC210171).

References

1	Atkinson EG, Adaway M, Horan DJ, Korff C, Klunk A, Orr AL, Ratz K, Bellido T, Plotkin LI, Robling AG and Bidwell JP: Conditional loss of Nmp4 in mesenchymal stem progenitor cells enhances PTH-induced bone formation. J Bone Miner Res. 38:70–85. 2023. View Article : Google Scholar
2	Wang J, Shu B, Tang DZ, Li CG, Xie XW, Jiang LJ, Jiang XB, Chen BL, Lin XC, Wei X, et al: The prevalence of osteoporosis in China, a community based cohort study of osteoporosis. Front Public Health. 11:10840052023. View Article : Google Scholar : PubMed/NCBI
3	Kobayashi H, Ito N, Nakai Y, Katoh H, Okajima K, Zhang L, Tsuda Y and Tanaka S: Patterns of symptoms and insufficiency fractures in patients with tumour-induced osteomalacia. Bone Joint J. 105-B:568–574. 2023. View Article : Google Scholar : PubMed/NCBI
4	Yang Z, Xing D, Dong Z, Wei J, Zhang L, Gao S and Li W: Epidemiological investigation of 387 individuals over 65 years old with osteoporotic fractures. Altern Ther Health Med. 29:207–211. 2023.PubMed/NCBI
5	Ju G and Liu X: A nomogram prediction model for refracture in elderly patients with osteoporotic vertebral compression fractures after percutaneous vertebroplasty. Eur Spine J. 32:3919–3926. 2023. View Article : Google Scholar
6	Deosthale P, Balanta-Melo J, Creecy A, Liu C, Marcial A, Morales L, Cridlin J, Robertson S, Okpara C, Sanchez DJ, et al: Fragile X Messenger Ribonucleoprotein 1 (FMR1), a novel inhibitor of osteoblast/osteocyte differentiation, regulates bone formation, mass, and strength in young and aged male and female mice. Bone Res. 11:252023. View Article : Google Scholar : PubMed/NCBI
7	Zhang C, Li H, Li J, Hu J, Yang K and Tao L: Oxidative stress: A common pathological state in a high-risk population for osteoporosis. Biomed Pharmacother. 163:1148342023. View Article : Google Scholar : PubMed/NCBI
8	Agliardi C, Guerini FR, Bolognesi E, Zanzottera M and Clerici M: VDR gene single nucleotide polymorphisms and autoimmunity: A narrative review. Biology (Basel). 12:9162023.
9	Talib WH, Ahmed Jum'AH DA, Attallah ZS, Jallad MS, Al Kury LT, Hadi RW and Mahmod AI: Role of vitamins A, C, D, E in cancer prevention and therapy: Therapeutic potentials and mechanisms of action. Front Nutr. 10:12818792024. View Article : Google Scholar : PubMed/NCBI
10	Prieto-de Lima TS, Rojas-Jimenez K and Vaglio C: Strategy for optimizing vitamin B12 production in pseudomonas putida KT2440 using metabolic modeling. Metabolites. 14:6362024. View Article : Google Scholar : PubMed/NCBI
11	Rizzi F, Panniello A, Comparelli R, Arduino I, Fanizza E, Iacobazzi RM, Perrone MG, Striccoli M, Curri ML, Scilimati A, et al: Luminescent alendronic acid-conjugated micellar nanostructures for potential application in the bone-targeted delivery of cholecalciferol. Molecules. 29:23672024. View Article : Google Scholar : PubMed/NCBI
12	Parhiala M, Ukkonen M, Sand J and Laukkarinen J: Osteoporosis and sarcopenia are common and insufficiently diagnosed among chronic pancreatitis patients. BMC Gastroenterol. 23:1242023. View Article : Google Scholar : PubMed/NCBI
13	Kirby BJ, Ma Y, Martin HM, Buckle Favaro KL, Karaplis AC and Kovacs CS: Upregulation of calcitriol during pregnancy and skeletal recovery after lactation do not require parathyroid hormone. J Bone Miner Res. 28:1987–2000. 2013. View Article : Google Scholar
14	Rondanelli M, Tartara A, Fossari F, Vecchio V, Faliva MA, Naso M, Perna S, Nichetti M and Peroni G: Adequate intake and supplementation of B vitamins, in particular folic acid, can play a protective role in bone health. Curr Aging Sci. 15:110–120. 2022. View Article : Google Scholar
15	Yang K, Cao F, Xue Y, Tao L and Zhu Y: Three classes of antioxidant defense systems and the development of postmenopausal osteoporosis. Front Physiol. 13:8402932022. View Article : Google Scholar :
16	Salma, Ahmad SS, Karim S, Ibrahim IM, Alkreathy HM, Alsieni M and Khan MA: Effect of vitamin K on bone mineral density and fracture risk in adults: Systematic review and meta-analysis. Biomedicines. 10:10482022. View Article : Google Scholar
17	Chen G, Weiskirchen S and Weiskirchen R: Vitamin A: Too good to be bad? Front Pharmacol. 14:11863362023. View Article : Google Scholar :
18	Yee MMF, Chin KY, Ima-Nirwana S and Wong SK: Vitamin A and bone health: A review on current evidence. Molecules. 26:17572021. View Article : Google Scholar :
19	Tanumihardjo SA, Gannon BM, Kaliwile C, Chileshe J and Binkley NC: Restricting vitamin A intake increases bone formation in Zambian children with high liver stores of vitamin. Arch Osteoporos. 14:722019. View Article : Google Scholar
20	Baybutt RC, Standard JT, Dim D, Quinn T, Hamdan H, Lin D, Kunz K, Bomstein ZS, Estorge BJ, Herndon B, et al: Cod liver oil, but not retinoic acid, treatment restores bone thickness in a vitamin A-deficient rat. Nutrients. 14:4862022. View Article : Google Scholar : PubMed/NCBI
21	Lind T, Lugano R, Gustafson AM, Norgård M, van Haeringen A, Dimberg A, Melhus H, Robertson SP and Andersson G: Bones in human CYP26B1 deficiency and rats with hypervitaminosis A phenocopy Vegfa overexpression. Bone Rep. 9:27–36. 2018. View Article : Google Scholar
22	Lionikaite V, Henning P, Drevinge C, Shah FA, Palmquist A, Wikström P, Windahl SH and Lerner UH: Vitamin A decreases the anabolic bone response to mechanical loading by suppressing bone formation. FASEB J. 33:5237–5247. 2019. View Article : Google Scholar
23	Zhang X, Huang J, Zhou Y, Hong Z, Lin X, Chen S, Ye Y and Zhang Z: Vitamin A nutritional status is a key determinant of bone mass in children. Nutrients. 14:46942022. View Article : Google Scholar : PubMed/NCBI
24	Fraher D, Mann RJ, Dubuisson MJ, Ellis MK, Yu T, Walder K, Ward AC, Winkler C and Gibert Y: The endocannabinoid system and retinoic acid signaling combine to influence bone growth. Mol Cell Endocrinol. 529:1112672021. View Article : Google Scholar :
25	Zhang S, Chen X, Hu Y, Wu J, Cao Q, Chen S and Gao Y: All-trans retinoic acid modulates Wnt3A-induced osteogenic differentiation of mesenchymal stem cells via activating the PI3K/AKT/GSK3β signalling pathway. Mol Cell Endocrinol. 422:243–253. 2016. View Article : Google Scholar
26	Navarro-Valverde C, Caballero-Villarraso J, Mata-Granados JM, Casado-Díaz A, Sosa-Henríquez M, Malouf-Sierra J, Nogués-Solán X, Rodríguez-Mañas L, Cortés-Gil X, Delgadillo-Duarte J and Quesada-Gómez JM: High serum retinol as a relevant contributor to low bone mineral density in postmenopausal osteoporotic women. Calcif Tissue Int. 102:651–656. 2018. View Article : Google Scholar
27	Zhuang Y, Sun X, Liu B, Hou H and Sun Y: Effects of rambutan peel (nepheliumlappaceum) PhenolicExtract on RANKL-induced differentiation of RAW264.7 cells into osteoclasts and retinoic acid-induced osteoporosis in rats. Nutrients. 12:8832020. View Article : Google Scholar : PubMed/NCBI
28	Wang S, Bi W, Liu Y, Cheng J, Sun W, Wu G and Xu X: The antagonist of retinoic acid receptor α, ER-50891 antagonizes the inhibitive effect of all-trans retinoic acid and rescues bone morphogenetic protein 2-induced osteoblastogenic differentiation. Drug Des Devel Ther. 14:297–308. 2020. View Article : Google Scholar :
29	Zhao S, Niu F, Xu CY, Liu Y, Ye L, Bi GB, Chen L, Tian G and Nie TH: Diosgenin prevents bone loss on retinoic acid-induced osteoporosis in rats. Ir J Med Sci. 185:581–587. 2016. View Article : Google Scholar
30	Liu RH, Kang X, Xu LP, Nian HL, Yang XW, Shi HT and Wang XJ: Effects of the combined extracts of Herba Epimedii and Fructus Ligustri Lucidi on bone mineral content and bone turnover in osteoporotic rats. BMC Complement Altern Med. 15:1122015. View Article : Google Scholar
31	Krutzen CLJM, Roa LA, Bloemen M and Von den Hoff JW: Excess vitamin a might contribute to submucous clefting by inhibiting WNT-mediated bone formation. Orthod Craniofac Res. 26:132–139. 2023. View Article : Google Scholar
32	Charkos TG, Liu Y, Oumer KS, Vuong AM and Yang S: Effects of β-carotene intake on the risk of fracture: A Bayesian meta-analysis. BMC Musculoskelet Disord. 21:7112020. View Article : Google Scholar
33	Gao SS and Zhao Y: The effects of β-carotene on osteoporosis: A systematic review and meta-analysis of observational studies. Osteoporos Int. 34:627–639. 2023. View Article : Google Scholar
34	Ahn TK, Kim JO, An HJ, Park HS, Choi UY, Sohn S, Kim KT, Kim NK and Han IB: 3′-UTR polymorphisms of vitamin B-related genes are associated with osteoporosis and osteoporotic vertebral compression fractures (OVCFs) in postmenopausal women. Genes (Basel). 11:6122020. View Article : Google Scholar
35	Dai Z and Koh WP: B-vitamins and bone health-a review of the current evidence. Nutrients. 7:3322–3346. 2015. View Article : Google Scholar : PubMed/NCBI
36	Zhang L, Jiao G, You Y, Li X, Liu J, Sun Z, Li Q, Dai Z, Ma J, Zhou H, et al: Arginine methylation of PPP1CA by CARM1 regulates glucose metabolism and affects osteogenic differentiation and osteoclastic differentiation. Clin Transl Med. 13:e13692023. View Article : Google Scholar
37	Ma Q, Liang M, Wang Y, Ding N, Wu Y, Duan L, Yu T, Lu Y, Xu J, Kang F and Dou C: Non-coenzyme role of vitamin B1 in RANKL-induced osteoclastogenesis and ovariectomy induced osteoporosis. J Cell Biochem. 121:3526–3536. 2020. View Article : Google Scholar : PubMed/NCBI
38	Wan M, Wu H, Wang X, Gu Y, Meng G, Zhang Q, Liu L, Zhang J, Sun S, Jia Q, et al: There is a significantly inverse relationship between dietary riboflavin intake and prevalence of osteoporosis in women but not in men: Results from the TCLSIH cohort study. Front Nutr. 10:11120282023. View Article : Google Scholar
39	Guo M and Zhang J: Vitamin B₂ prevents glucocorticoid-caused damage of blood vessels in osteonecrosis of the femoral head. Biomed Res Int. 2022:40061842022. View Article : Google Scholar
40	Chaves Neto AH, Yano CL, Paredes-Gamero EJ, Machado D, Justo GZ, Peppelenbosch MP and Ferreira CV: Riboflavin and photoproducts in MC3T3-E1 differentiation. Toxicol In Vitro. 24:1911–1919. 2010. View Article : Google Scholar : PubMed/NCBI
41	Welan R: Effect of vitamin B6 on osteoporosis fracture. J Bone Metab. 30:141–147. 2023. View Article : Google Scholar : PubMed/NCBI
42	Wang J, Chen L, Zhang Y, Li CG, Zhang H, Wang Q, Qi X, Qiao L, Da WW, Cui XJ, et al: Association between serum vitamin B₆ concentration and risk of osteoporosis in the middle-aged and older people in China: A cross-sectional study. BMJ Open. 9:e0281292019. View Article : Google Scholar
43	Lee JS, Kim K, Park JP, Cho SW and Lee H: Role of pyridoxal 5′-phosphate at the titanium implant interface in vivo: Increased hemophilicity, inactive platelet adhesion, and osteointegration. Adv Healthc Mater. 6:16009622017. View Article : Google Scholar
44	Dodds RA, Catterall A, Bitensky L and Chayen J: Abnormalities in fracture healing induced by vitamin B6-deficiency in rats. Bone. 7:489–495. 1986. View Article : Google Scholar
45	Santos C, Gomes P, Duarte JA, Almeida MM, Costa MEV and Fernandes MH: Development of hydroxyapatite nanoparticles loaded with folic acid to induce osteoblastic differentiation. Int J Pharm. 516:185–195. 2017. View Article : Google Scholar
46	Georgiou KR, Nadhanan RR, Fan CM and Xian CJ: Methotrexate-induced bone marrow adiposity is mitigated by folinic acid supplementation through the regulation of Wnt/β-catenin signalling. J Cell Physiol. 230:648–656. 2015. View Article : Google Scholar
47	Clements M, Heffernan M, Ward M, Hoey L, Doherty LC, Hack Mendes R, Clarke MM, Hughes CF, Love I, Murphy S, et al: A 2-year randomized controlled trial with low-dose B-vitamin supplementation shows benefits on bone mineral density in adults with lower B12 status. J Bone Miner Res. 37:2443–2455. 2022. View Article : Google Scholar
48	Hussain SIB, AlKhenizan A, Mahmoud A and Qashlaq H: The correlation between vitamin B12 and folate levels and bone mineral density among the Saudi population in a primary care setting. J Family Med Prim Care. 12:1063–1068. 2023. View Article : Google Scholar : PubMed/NCBI
49	Ates Bulut E, Soysal P, Aydin AE, Dokuzlar O, Kocyigit SE and Isik AT: Vitamin B12 deficiency might be related to sarcopenia in older adults. Exp Gerontol. 95:136–140. 2017. View Article : Google Scholar : PubMed/NCBI
50	Stone KL, Lui LY, Christen WG, Troen AM, Bauer DC, Kado D, Schambach C, Cummings SR and Manson JE: Effect of combination folic acid, vitamin B₆, and vitamin B₁₂ fracture risk in women: A randomized, controlled trial. J supplementation on Bone Miner Res. 32:2331–2338. 2017. View Article : Google Scholar
51	Herrmann M, Schmidt J, Umanskaya N, Colaianni G, Al Marrawi F, Widmann T, Zallone A, Wildemann B and Herrmann W: Stimulation of osteoclast activity by low B-vitamin concentrations. Bone. 41:584–591. 2007. View Article : Google Scholar
52	Su S, Zhang D, Liu J, Zhao H, Tang X, Che H, Wang Q, Ren W and Zhen D: Folate ameliorates homocysteine-induced osteoblast dysfunction by reducing endoplasmic reticulum stress-activated PERK/ATF-4/CHOP pathway in MC3T3-E1 cells. J Bone Miner Metab. 40:422–433. 2022. View Article : Google Scholar : PubMed/NCBI
53	Rondanelli M, Peroni G, Fossari F, Vecchio V, Faliva MA, Naso M, Perna S, Di Paolo E, Riva A, Petrangolini G, et al: Evidence of a positive link between consumption and supplementation of ascorbic acid and bone mineral density. Nutrients. 13:10122021. View Article : Google Scholar
54	Yang K, Cao F, Qiu S, Jiang W, Tao L and Zhu Y: Metformin promotes differentiation and attenuates H₂O₂-induced oxidative damage of osteoblasts via the PI3K/AKT/Nrf2/HO-1 pathway. Front Pharmacol. 13:8298302022. View Article : Google Scholar
55	Jain SK, McLean WE, Stevens CM and Dhawan R: The positive association of plasma levels of vitamin C and inverse association of VCAM-1 and total adiponectin with bone mineral density in subjects with diabetes. Nutrients. 14:38932022. View Article : Google Scholar
56	Malmir H, Shab-Bidar S and Djafarian K: Vitamin C intake in relation to bone mineral density and risk of hip fracture and osteoporosis: A systematic review and meta-analysis of observational studies. Br J Nutr. 119:847–858. 2018. View Article : Google Scholar
57	Zeng LF, Luo MH, Liang GH, Yang WY, Xiao X, Wei X, Yu J, Guo D, Chen HY, Pan JK, et al: Can dietary intake of vitamin C-oriented foods reduce the risk of osteoporosis, fracture, and BMD loss? Systematic review with meta-analyses of recent studies. Front Endocrinol (Lausanne). 10:8442020. View Article : Google Scholar : PubMed/NCBI
58	Sarkar N, Morton H and Bose S: Effects of vitamin C on osteoblast proliferation and osteosarcoma inhibition using plasma coated hydroxyapatite on titanium implants. Surf Coat Technol. 394:1257932020. View Article : Google Scholar
59	Xie Y, Bao Z, Wang Z, Du D, Chen G, Liu C, Wang H, Feng N, Xiao X, Wang S, et al: Magnesium ascorbyl phosphate promotes bone formation via CaMKII signaling. J Bone Miner Res. 38:1015–1031. 2023. View Article : Google Scholar : PubMed/NCBI
60	Choi HK, Kim GJ, Yoo HS, Song DH, Chung KH, Lee KJ, Koo YT and An JH: Vitamin C activates osteoblastogenesis and inhibits osteoclastogenesis via Wnt/β-catenin/ATF4 signaling pathways. Nutrients. 11:5062019. View Article : Google Scholar
61	Smith-Cortinez N, Fagundes RR, Gomez V, Kong D, de Waart DR, Heegsma J, Sydor S, Olinga P, de Meijer VE, Taylor CT, et al: Collagen release by human hepatic stellate cells requires vitamin C and is efficiently blocked by hydroxylase inhibition. FASEB J. 35:e212192021. View Article : Google Scholar
62	Bellissimo MP, Roberts JL, Jones DP, Liu KH, Taibl KR, Uppal K, Weitzmann MN, Pacifici R, Drissi H, Ziegler TR and Alvarez JA: Metabolomic associations with serum bone turnover markers. Nutrients. 12:31612020. View Article : Google Scholar
63	Okajima LS, Martinez EF, Pinheiro IF, Fonseca Silva AS and Demasi APD: Effect of sodium ascorbyl phosphate on osteoblast viability and differentiation. J Periodontal Res. 55:660–666. 2020. View Article : Google Scholar : PubMed/NCBI
64	Liu G, Li W, Zhang L, Zhou C and Cong R: The role of vitamin D on rotator cuff tear with osteoporosis. Front Endocrinol (Lausanne). 13:10178352022. View Article : Google Scholar
65	Ryan BA, McGregor NE, Kirby BJ, Al-Tilissi A, Poulton IJ, Sims NA and Kovacs CS: Calcitriol-dependent and -independent regulation of intestinal calcium absorption, osteoblast function, and skeletal mineralization during lactation and recovery in mice. J Bone Miner Res. 37:2483–2497. 2022. View Article : Google Scholar : PubMed/NCBI
66	Beckett E: More than bone health: The many roles for vitamin D. Nutrients. 12:23882020. View Article : Google Scholar : PubMed/NCBI
67	Imai K, Neuman MW, Kawase T and Saito S: Calcium in osteoblast-enriched bone cells. Bone. 13:217–223. 1992. View Article : Google Scholar : PubMed/NCBI
68	Al Saedi A, Myers DE, Stupka N and Duque G: 1,25(OH)₂D₃ ameliorates palmitate-induced lipotoxicity in human primary osteoblasts leading to improved viability and function. Bone. 141:1156722020. View Article : Google Scholar
69	Posa F, Di Benedetto A, Colaianni G, Cavalcanti-Adam EA, Brunetti G, Porro C, Trotta T, Grano M and Mori G: Vitamin D effects on osteoblastic differentiation of mesenchymal stem cells from dental tissues. Stem Cells Int. 2016:91508192016. View Article : Google Scholar :
70	Kanemoto Y, Iwaki M, Sawada T, Nojiri K, Kurokawa T, Tsutsumi R, Nagasawa K and Kato S: Advances in the administration of vitamin D analogues to support bone health and treat chronic diseases. J Bone Metab. 30:219–229. 2023. View Article : Google Scholar : PubMed/NCBI
71	Mansell JP, Tanatani A and Kagechika H: An N-cyanoamide derivative of lithocholic acid co-operates with lysophosphatidic acid to promote human osteoblast (MG63) differentiation. Biomolecules. 13:11132023. View Article : Google Scholar : PubMed/NCBI
72	Nakamichi Y, Liu Z, Mori T, He Z, Yasuda H, Takahashi N and Udagawa N: The vitamin D receptor in osteoblastic cells but not secreted parathyroid hormone is crucial for soft tissue calcification induced by the proresorptive activity of 1,25(OH)₂D₃. J Steroid Biochem Mol Biol. 232:1063512023. View Article : Google Scholar
73	Mondockova V, Kovacova V, Zemanova N, Babikova M, Martiniakova M, Galbavy D and Omelka R: Vitamin D receptor gene polymorphisms affect osteoporosis-related traits and response to antiresorptive therapy. Genes (Basel). 14:1932023. View Article : Google Scholar : PubMed/NCBI
74	Haeri NS, Perera S and Greenspan SL: The association of vitamin D with bone microarchitecture, muscle strength, and mobility performance in older women in long-term care. Bone. 176:1168672023. View Article : Google Scholar : PubMed/NCBI
75	Waterhouse M, Ebeling PR, McLeod DSA, English D, Romero BD, Baxter C, Armstrong BK, Hartel G, Kimlin M, O'Connell RL, et al: The effect of monthly vitamin D supplementation on fractures: a tertiary outcome from the population-based, double-blind, randomised, placebo-controlled D-health trial. Lancet Diabetes Endocrinol. 11:324–332. 2023. View Article : Google Scholar : PubMed/NCBI
76	Gallagher JC and Rosen CJ: Vitamin D: 100 Years of discoveries, yet controversy continues. Lancet Diabetes Endocrinol. 11:362–374. 2023. View Article : Google Scholar
77	Mansur JL, Oliveri B, Giacoia E, Fusaro D and Costanzo PR: Vitamin D: Before, during and after pregnancy: Effect on neonates and children. Nutrients. 14:19002022. View Article : Google Scholar
78	Zainal Z, Khaza'ai H, Kutty Radhakrishnan A and Chang SK: Therapeutic potential of palm oil vitamin E-derived tocotrienols in inflammation and chronic diseases: Evidence from preclinical and clinical studies. Food Res Int. 156:1111752022. View Article : Google Scholar : PubMed/NCBI
79	Wong SK, Chin KY and Ima-Nirwana S: The effects of tocotrienol on bone peptides in a rat model of osteoporosis induced by metabolic syndrome: The possible communication between bone cells. Int J Environ Res Public Health. 16:33132019. View Article : Google Scholar :
80	Holvik K, Gjesdal CG, Tell GS, Grimnes G, Schei B, Apalset EM, Samuelsen SO, Blomhoff R, Michaëlsson K and Meyer HE: Low serum concentrations of alpha-tocopherol are associated with increased risk of hip fracture. A NOREPOS study. Osteoporos Int. 25:2545–2554. 2014. View Article : Google Scholar : PubMed/NCBI
81	Xu W, Li Y, Feng R, He P and Zhang Y: γ-Tocotrienol induced the proliferation and differentiation of MC3T3-E1 cells through the stimulation of the Wnt/β-catenin signaling pathway. Food Funct. 13:398–410. 2022. View Article : Google Scholar
82	Wan Hasan WN, Chin KY, Abd Ghafar N and Soelaiman IN: Annatto-derived tocotrienol promotes mineralization of MC3T3-E1 cells by enhancing BMP-2 protein expression via inhibiting RhoA activation and HMG-CoA reductase gene expression. Drug Des Devel Ther. 14:969–976. 2020. View Article : Google Scholar : PubMed/NCBI
83	Wan Hasan WN, Abd Ghafar N, Chin KY and Ima-Nirwana S: Annatto-derived tocotrienol stimulates osteogenic activity in preosteoblastic MC3T3-E1 cells: A temporal sequential study. Drug Des Devel Ther. 12:1715–1726. 2018. View Article : Google Scholar : PubMed/NCBI
84	Hagan ML, Bahraini A, Pierce JL, Bass SM, Yu K, Elsayed R, Elsalanty M, Johnson MH, McNeil A, McNeil PL and McGee-Lawrence ME: Inhibition of osteocyte membrane repair activity via dietary vitamin E deprivation impairs osteocyte survival. Calcif Tissue Int. 104:224–234. 2019. View Article : Google Scholar :
85	Mohamad NV, Soelaiman IN and Chin KY: Effects of tocotrienol from Bixa orellana (annatto) on bone histomorphometry in a male osteoporosis model induced by buserelin. Biomed Pharmacother. 103:453–462. 2018. View Article : Google Scholar : PubMed/NCBI
86	Mohamad Hazir NS, Yahaya NHM, Zawawi MSF, Damanhuri HA, Mohamed N and Alias E: Changes in metabolism and mitochondrial bioenergetics during polyethylene-induced osteoclastogenesis. Int J Mol Sci. 23:83312022. View Article : Google Scholar : PubMed/NCBI
87	Vallibhakara SAO, Nakpalat K, Sophonsritsuk A, Tantitham C and Vallibhakara O: Effect of vitamin E supplement on bone turnover markers in postmenopausal osteopenic women: A double-blind, randomized, placebo-controlled trial. Nutrients. 13:42262021. View Article : Google Scholar : PubMed/NCBI
88	Fujiwara Y, Ko Y, Sonoda M, Ichi I and Ishikawa T: Effects of vitamin E and dietary conditions on the differentiation and maturation of osteoclast. J Nutr Sci Vitaminol (Tokyo). 68:73–77. 2022. View Article : Google Scholar : PubMed/NCBI
89	Piscaer I, Janssen R, Franssen FME, Schurgers LJ and Wouters EFM: The pleiotropic role of vitamin K in multimorbidity of chronic obstructive pulmonary disease. J Clin Med. 12:12612023. View Article : Google Scholar :
90	He J, Xie H, Yan C, Sun Y, Xu Z and Zhang X: Genetic variation in VKORC1 and risk for osteoporosis. Arch Med Res. 52:211–216. 2021. View Article : Google Scholar
91	Urano A, Hotta M, Ohwada R and Araki M: Vitamin K deficiency evaluated by serum levels of undercarboxylated osteocalcin in patients with anorexia nervosa with bone loss. Clin Nutr. 34:443–448. 2015. View Article : Google Scholar
92	Lee AS, Sung MJ, Son SJ, Han AR, Hong SM and Lee SH: Effect of menaquinone-4 on receptor activator of nuclear factor κB ligand-induced osteoclast differentiation and ovariectomy-induced bone loss. J Med Food. 26:128–134. 2023.
93	Popa DS, Bigman G and Rusu ME: The role of vitamin K in humans: Implication in aging and age-associated diseases. Antioxidants (Basel). 10:5662021. View Article : Google Scholar
94	Alonso N, Meinitzer A, Fritz-Petrin E, Enko D and Herrmann M: Role of vitamin K in bone and muscle metabolism. Calcif Tissue Int. 112:178–196. 2023. View Article : Google Scholar
95	Stock M and Schett G: Vitamin K-dependent proteins in skeletal development and disease. Int J Mol Sci. 22:93282021. View Article : Google Scholar
96	Wang J, Shao L, Wu X, Liu C, Ni S, Dai T, Liu H and Zhao H: Electrospun sandwich mesh structures loaded with naringenin and vitamin K₂ polycaprolactone/gelatin nanofibers synergistically promote bone regeneration. Mater Today Bio. 23:1007942023. View Article : Google Scholar
97	Giordani C, Matacchione G, Giuliani A, Valli D, Scarpa ES, Antonelli A, Sabbatinelli J, Giacchetti G, Sabatelli S, Olivieri F and Rippo MR: Pro-osteogenic and anti-inflammatory synergistic effect of orthosilicic acid, vitamin K2, curcumin, polydatin and quercetin combination in young and senescent bone marrow-derived mesenchymal stromal cells. Int J Mol Sci. 24:88202023. View Article : Google Scholar :
98	Wang H, Li L, Zhang N and Ma Y: Vitamin K2 improves osteogenic differentiation by inhibiting STAT1 via the Bcl-6 and IL-6/JAK in C3H10 T1/2 clone 8 cells. Nutrients. 14:29342022. View Article : Google Scholar : PubMed/NCBI
99	Castaneda M, Strong JM, Alabi DA and Hernandez CJ: The gut microbiome and bone strength. Curr Osteoporos Rep. 18:677–683. 2020. View Article : Google Scholar : PubMed/NCBI
100	Ozaki D, Kubota R, Maeno T, Abdelhakim M and Hitosugi N: Association between gut microbiota, bone metabolism, and fracture risk in postmenopausal Japanese women. Osteoporos Int. 32:145–156. 2021. View Article : Google Scholar
101	Li W, Zhang S, Liu J, Liu Y and Liang Q: Vitamin K2 stimulates MC3T3-E1 osteoblast differentiation and mineralization through autophagy induction. Mol Med Rep. 19:3676–3684. 2019.
102	AlHajri L, Ayoub A, Ahmed H and AlMulla M: Effect of vitamin K2 alone or in combination on various bone turnover markers amongst postmenopausal females. J Bone Metab. 28:11–26. 2021. View Article : Google Scholar : PubMed/NCBI
103	Capozzi A, Scambia G and Lello S: Calcium, vitamin D, vitamin K2, and magnesium supplementation and skeletal health. Maturitas. 140:55–63. 2020. View Article : Google Scholar : PubMed/NCBI
104	Marietta M, Coluccio V, Boriani G and Luppi M: Effects of anti-vitamin k oral anticoagulants on bone and cardiovascular health. Eur J Intern Med. 79:1–11. 2020. View Article : Google Scholar
105	Grili PPDF, Vidigal CV, Cruz GFD, Albergaria BH, Marques-Rocha JL, Pereira TSS and Guandalini VR: Nutrient patterns and risk of osteopenia in postmenopausal women. Nutrients. 15:16702023. View Article : Google Scholar : PubMed/NCBI
106	Zhang R, Ni Z, Wei M, Cui Y, Zhou H, Di D and Wang Q: Composite dietary antioxidant intake and osteoporosis likelihood in premenopausal and postmenopausal women: A population-based study in the United States. Menopause. 30:529–538. 2023.
107	Nguyen HD: Interactions between nutrient intake and comorbidities for quality of life in premenopausal and postmenopausal women. Menopause. 29:1285–1295. 2022. View Article : Google Scholar
108	Bakker MF, Peeters PH, Klaasen VM, Bueno-de-Mesquita HB, Jansen EH, Ros MM, Travier N, Olsen A, Tjønneland A, Overvad K, et al: Plasma carotenoids, vitamin C, tocopherols, and retinol and the risk of breast cancer in the European prospective investigation into cancer and nutrition cohort. Am J Clin Nutr. 103:454–464. 2016. View Article : Google Scholar : PubMed/NCBI
109	Feskanich D, Singh V, Willett WC and Colditz GA: Vitamin A intake and hip fractures among postmenopausal women. JAMA. 287:47–54. 2002. View Article : Google Scholar : PubMed/NCBI
110	El Maghraoui A, Ghozlani I, Mounach A, Rezqi A, Oumghar K, Achemlal L, Bezza A and Ouzzif Z: Homocysteine, folate, and vitamin B12 levels and vertebral fracture risk in postmenopausal women. J Clin Densitom. 15:328–333. 2012. View Article : Google Scholar
111	Salari P, Abdollahi M, Heshmat R, Meybodi HA and Razi F: Effect of folic acid on bone metabolism: A randomized double blind clinical trial in postmenopausal osteoporotic women. Daru. 22:622014. View Article : Google Scholar
112	Zhang H, Tao X and Wu J: Association of homocysteine, vitamin B12, and folate with bone mineral density in postmenopausal women: a meta-analysis. Arch Gynecol Obstet. 289:1003–1009. 2014. View Article : Google Scholar
113	Murray AA, Molinek MD, Baker SJ, Kojima FN, Smith MF, Hillier SG and Spears N: Role of ascorbic acid in promoting follicle integrity and survival in intact mouse ovarian follicles in vitro. Reproduction. 121:89–96. 2001. View Article : Google Scholar : PubMed/NCBI
114	McSorley PT, Young IS, Bell PM, Fee JP and McCance DR: Vitamin C improves endothelial function in healthy estrogen-deficient postmenopausal women. Climacteric. 6:238–247. 2003. View Article : Google Scholar : PubMed/NCBI
115	Moreau KL, Hildreth KL, Klawitter J, Blatchford P and Kohrt WM: Decline in endothelial function across the menopause transition in healthy women is related to decreased estradiol and increased oxidative stress. Geroscience. 42:1699–1714. 2020. View Article : Google Scholar
116	Sugiura M, Nakamura M, Ogawa K, Ikoma Y and Yano M: High vitamin C intake with high serum β-cryptoxanthin associated with lower risk for osteoporosis in post-menopausal Japanese female subjects: Mikkabi cohort study. J Nutr Sci Vitaminol (Tokyo). 62:185–191. 2016. View Article : Google Scholar
117	Mangano KM, Noel SE, Dawson-Hughes B and Tucker KL: Sufficient plasma vitamin C is related to greater bone mineral density among postmenopausal women from the boston puerto rican health study. J Nutr. 151:3764–3772. 2021. View Article : Google Scholar : PubMed/NCBI
118	Bae YJ: Fruit intake and osteosarcopenic obesity in Korean postmenopausal women aged 50-64 years. Maturitas. 134:41–46. 2020. View Article : Google Scholar : PubMed/NCBI
119	Hassanein MM, Huri HZ, Abduelkarem AR and Baig K: Therapeutic effects of vitamin D on vaginal, sexual, and urological functions in postmenopausal women. Nutrients. 15:38042023. View Article : Google Scholar : PubMed/NCBI
120	Alinia T, Sabour S, Hashemipour M, Hovsepian S, Pour HR and Jahanfar S: Relationship between vitamin D levels and age of menopause and reproductive lifespan: Analysis based on the National health and nutrition examination survey (NHANES) 2001-2018. Eur J Obstet Gynecol Reprod Biol. 289:183–189. 2023. View Article : Google Scholar : PubMed/NCBI
121	Shi JW, Wu JN, Zhu XY, Zhou WH, Yang JY and Li MQ: Association of serum 25-hydroxyvitamin D levels with all-cause and cause-specific mortality among postmenopausal females: Results from NHANES. J Transl Med. 21:6292023. View Article : Google Scholar
122	Begga A, Mehaoudi RI, Ghozlani A, Azzoug S and Soltani Y: The risk of metabolic syndrome is associated with vitamin D and inflammatory status in premenopausal and postmenopausal Algerian women. Ir J Med Sci. 193:615–626. 2024. View Article : Google Scholar
123	Anagnostis P, Livadas S, Goulis DG, Bretz S, Ceausu I, Durmusoglu F, Erkkola R, Fistonic I, Gambacciani M, Geukes M, et al: EMAS position statement: Vitamin D and menopausal health. Maturitas. 169:2–9. 2023. View Article : Google Scholar
124	Chan CY, Subramaniam S, Mohamed N, Muhammad N, Ramli FF, Ima-Nirwana S and Chin KY: Circulating biomarkers related to osteocyte and calcium homeostasis between postmenopausal women with and without osteoporosis. Endocr Metab Immune Disord Drug Targets. 21:2273–2280. 2021. View Article : Google Scholar : PubMed/NCBI
125	Mata-Granados JM, Cuenca-Acevedo JR, Luque de Castro MD, Holick MF and Quesada-Gómez JM: Vitamin D insufficiency together with high serum levels of vitamin A increases the risk for osteoporosis in postmenopausal women. Arch Osteoporos. 8:1242013. View Article : Google Scholar : PubMed/NCBI
126	Li C, Liang C, Kong Z, Su Y, Ren W, Dong H, Wu Y, Yang N, Liu R, Wu J and Zheng Y: Determination of vitamin K1, MK-4, MK-7, and D levels in human serum of postmenopausal osteoporosis women based on high stability LC-MS/MS: MK-7 may be a new marker of bone metabolism. Ann Nutr Metab. 79:334–342. 2023. View Article : Google Scholar
127	Jeong C, Ha J, Yoo JI, Lee YK, Kim JH, Ha YC, Min YK, Byun DW, Baek KH and Chung HY: Effects of bazedoxifene/vitamin D combination therapy on serum vitamin D levels and bone turnover markers in postmenopausal women with osteopenia: A randomized controlled trial. J Bone Metab. 30:189–199. 2023. View Article : Google Scholar : PubMed/NCBI
128	Reis AR, Santos RKF, Dos Santos CB, Santos BDC, de Carvalho GB, Brandão-Lima PN, de Oliveira E Silva AM and Pires LV: Supplementation of vitamin D isolated or calcium-associated with bone remodeling and fracture risk in postmenopausal women without osteoporosis: A systematic review of randomized clinical trials. Nutrition. 116:1121512023. View Article : Google Scholar
129	Dell Aquila LP, Morales A, Moreira P, Cendoroglo MS, Elias RM and Dalboni MA: Prospective effects of cholecalciferol supplementation on irisin levels in sedentary postmenopausal women: A pilot study. J Clin Transl Endocrinol. 34:1003242023.PubMed/NCBI
130	Samare-Najaf M, Zal F and Safari S: Primary and secondary markers of doxorubicin-induced female infertility and the alleviative properties of quercetin and vitamin E in a rat model. Reprod Toxicol. 96:316–326. 2020. View Article : Google Scholar : PubMed/NCBI
131	Feduniw S, Korczyńska L, Górski K, Zgliczyńska M, Bączkowska M, Byrczak M, Kociuba J, Ali M and Ciebiera M: The effect of vitamin E supplementation in postmenopausal women-A systematic review. Nutrients. 15:1602022. View Article : Google Scholar
132	Ibrahim N, Mohd Noor H, Shuid AN, Mohamad S, Abdul Malik MM, Jayusman PA, Shuid AN and Naina Mohamed I: Osteoprotective effects in postmenopausal osteoporosis rat model: Oral tocotrienol vs intraosseous injection of tocotrienol-poly lactic-co-glycolic acid combination. Front Pharmacol. 12:7067472021. View Article : Google Scholar
133	Mohamad NV, Ima-Nirwana S and Chin KY: Self-emulsified annatto tocotrienol improves bone histomorphometric parameters in a rat model of oestrogen deficiency through suppression of skeletal sclerostin level and RANKL/OPG ratio. Int J Med Sci. 18:3665–3673. 2021. View Article : Google Scholar : PubMed/NCBI
134	Johnson SA, Feresin RG, Soung do Y, Elam ML and Arjmandi BH: Vitamin E suppresses ex vivo osteoclastogenesis in ovariectomized rats. Food Funct. 7:1628–1633. 2016. View Article : Google Scholar : PubMed/NCBI
135	Shen CL, Yang S, Tomison MD, Romero AW, Felton CK and Mo H: Tocotrienol supplementation suppressed bone resorption and oxidative stress in postmenopausal osteopenic women: A 12-week randomized double-blinded placebo-controlled trial. Osteoporos Int. 29:881–891. 2018. View Article : Google Scholar
136	Rangel LBA, de Siqueira D, Soares ODR, Santana HS, Miguel EC, da Cunha M, Oliveira ALA, Pedrosa DF, Resgala LCR, Neto HAR, et al: Vitamin K supplementation modulates bone metabolism and ultra-structure of ovariectomized mice. Cell Physiol Biochem. 51:356–374. 2018. View Article : Google Scholar
137	Wang H, Zhang N, Li L, Yang P and Ma Y: Menaquinone 4 reduces bone loss in ovariectomized mice through dual regulation of bone remodeling. Nutrients. 13:25702021. View Article : Google Scholar :
138	Wasilewski GB, Vervloet MG and Schurgers LJ: the bone-vasculature axis: Calcium supplementation and the role of vitamin K. Front Cardiovasc Med. 6:62019. View Article : Google Scholar
139	Jaghsi S, Hammoud T and Haddad S: Relation between circulating vitamin K1 and osteoporosis in the lumbar spine in syrian post-menopausal women. Open Rheumatol J. 12:1–9. 2018. View Article : Google Scholar : PubMed/NCBI
140	Moore AE, Kim E, Dulnoan D, Dolan AL, Voong K, Ahmad I, Gorska R, Harrington DJ and Hampson G: Serum vitamin K₁ (phylloquinone) is associated with fracture risk and hip strength in post-menopausal osteoporosis: A cross-sectional study. Bone. 141:1156302020. View Article : Google Scholar
141	Ma ML, Ma ZJ, He YL, Sun H, Yang B, Ruan BJ, Zhan WD, Li SX, Dong H and Wang YX: Efficacy of vitamin K2 in the prevention and treatment of postmenopausal osteoporosis: A systematic review and meta-analysis of randomized controlled trials. Front Public Health. 10:9796492022. View Article : Google Scholar :
142	Zhou M, Han S, Zhang W and Wu D: Efficacy and safety of vitamin K2 for postmenopausal women with osteoporosis at a long-term follow-up: Meta-analysis and systematic review. J Bone Miner Metab. 40:763–772. 2022. View Article : Google Scholar : PubMed/NCBI
143	Pan X, Ren Z, Liang W, Dong X, Li J, Wang L, Bhatia M, Pan LL and Sun J: Thiamine deficiency aggravates experimental colitis in mice by promoting glycolytic reprogramming in macrophages. Br J Pharmacol. 182:1897–1911. 2025. View Article : Google Scholar : PubMed/NCBI
144	Biegstraaten M, Mengel E, Maródi L, Petakov M, Niederau C, Giraldo P, Hughes D, Mrsic M, Mehta A, Hollak CEM and van Schaik IN: Peripheral neuropathy in adult type 1 Gaucher disease: A 2-year prospective observational study. Brain. 133:2909–2919. 2010. View Article : Google Scholar : PubMed/NCBI
145	Al-Daghri NM, Alharbi M, Wani K, Abd-Alrahman SH, Sheshah E and Alokail MS: Biochemical changes correlated with blood thiamine and its phosphate esters levels in patients with diabetes type 1 (DMT1). Int J Clin Exp Pathol. 8:13483–13488. 2015.
146	Al-Attas O, Al-Daghri N, Alokail M, Abd-Alrahman S, Vinodson B and Sabico S: Metabolic benefits of six-month thiamine supplementation in patients with and without diabetes mellitus type 2. Clin Med Insights Endocrinol Diabetes. 7:1–6. 2014. View Article : Google Scholar : PubMed/NCBI
147	Al Quran T, Khader A, Allan H, Al-Momani R, Aqel HT, Alsaleh M and Bataineh Z: Prevalence of vitamin B12 deficiency in type 2 diabetic patients taking metformin, a cross-sectional study in primary healthcare. Front Endocrinol (Lausanne). 14:12267982023. View Article : Google Scholar :
148	Ekeuku SO, Chong PN, Chan HK, Mohamed N, Froemming GRA and Okechukwu PN: Spirulina supplementation improves bone structural strength and stiffness in streptozocin-induced diabetic rats. J Tradit Complement Med. 12:225–234. 2021. View Article : Google Scholar
149	Toraman A, Arabaci T, Aytekin Z, Albayrak M and Bayir Y: Effects of vitamin C local application on ligature-induced periodontitis in diabetic rats. J Appl Oral Sci. 28:e202004442020. View Article : Google Scholar :
150	Mason SA, Della Gatta PA, Snow RJ, Russell AP and Wadley GD: Ascorbic acid supplementation improves skeletal muscle oxidative stress and insulin sensitivity in people with type 2 diabetes: Findings of a randomized controlled study. Free Radic Biol Med. 93:227–238. 2016. View Article : Google Scholar : PubMed/NCBI
151	Hao L, Lu A, Gao H, Niu J, Prabahar K, Seraj SS and Pan Y: The effects of vitamin D on markers of glucose and obesity in postmenopausal women: A meta-analysis of randomized controlled trials. Clin Ther. 45:913–920. 2023. View Article : Google Scholar : PubMed/NCBI
152	Ji Y, Geng N, Niu Y, Zhao H, Fei W, Chen S and Ren LP: Relationship between geriatric nutritional risk index and osteoporosis in type 2 diabetes in Northern China. BMC Endocr Disord. 22:3082022. View Article : Google Scholar :
153	Zhang J, Li Y, Lai D, Lu D, Lan Z, Kang J, Xu Y and Cai S: Vitamin D status is negatively related to insulin resistance and bone turnover in Chinese non-osteoporosis patients with type 2 diabetes: A retrospective cross-section research. Front Public Health. 9:7271322022. View Article : Google Scholar :
154	Luo W, Jiang Y, Yi Z, Wu Y, Gong P and Xiong Y: 1α,25-Dihydroxyvitamin D₃ promotes osteogenesis by down-regulating FGF23 in diabetic mice. J Cell Mol Med. 25:4148–4156. 2021. View Article : Google Scholar : PubMed/NCBI
155	Jiang Y, Luo W, Wang B, Yi Z, Gong P and Xiong Y: 1α,25-Dihydroxyvitamin D3 ameliorates diabetes-induced bone loss by attenuating FoxO1-mediated autophagy. J Biol Chem. 296:1002872021. View Article : Google Scholar
156	Xiong Y, Zhang Y, Guo Y, Yuan Y, Guo Q, Gong P and Wu Y: 1α,25-Dihydroxyvitamin D₃ increases implant osseointegration in diabetic mice partly through FoxO1 inactivation in osteoblasts. Biochem Biophys Res Commun. 494:626–633. 2017. View Article : Google Scholar
157	Shen CL, Kaur G, Wanders D, Sharma S, Tomison MD, Ramalingam L, Chung E, Moustaid-Moussa N, Mo H and Dufour JM: Annatto-extracted tocotrienols improve glucose homeostasis and bone properties in high-fat diet-induced type 2 diabetic mice by decreasing the inflammatory response. Sci Rep. 8:113772018. View Article : Google Scholar :
158	Jin C, Tan K, Yao Z, Lin BH, Zhang DP, Chen WK, Mao SM, Zhang W, Chen L, Lin Z, et al: A novel anti-osteoporosis mechanism of VK2: Interfering with ferroptosis via AMPK/SIRT1 pathway in type 2 diabetic osteoporosis. J Agric Food Chem. 71:2745–2761. 2023. View Article : Google Scholar
159	Poon CCW, Li RWS, Seto SW, Kong SK, Ho HP, Hoi MPM, Lee SMY, Ngai SM, Chan SW, Leung GPH and Kwan YW: In vitro vitamin K(2) and 1α,25-dihydroxyvitamin D(3) combination enhances osteoblasts anabolism of diabetic mice. Eur J Pharmacol. 767:30–40. 2015. View Article : Google Scholar
160	Carioca AAF, Verde SMM, Luzia LA, Rondó PHC, Latorre MRDO, Ellery THP and Damasceno NRT: Association of oxidative stress biomarkers with adiposity and clinical staging in women with breast cancer. Eur J Clin Nutr. 69:1256–1261. 2015. View Article : Google Scholar
161	Fenzl A, Kulterer OC, Spirk K, Mitulović G, Marculescu R, Bilban M, Baumgartner-Parzer S, Kautzky-Willer A, Kenner L, Plutzky J, et al: Intact vitamin A transport is critical for cold-mediated adipose tissue browning and thermogenesis. Mol Metab. 42:1010882020. View Article : Google Scholar : PubMed/NCBI
162	Daneshzad E, Farsad-Naeimi A, Heshmati J, Mirzaei K, Maghbooli Z and Keshavarz SA: The association between dietary antioxidants and adipokines level among obese women. Diabetes Metab Syndr. 13:1369–1373. 2019. View Article : Google Scholar : PubMed/NCBI
163	Högström M, Nordström A and Nordström P: Retinol, retinol-binding protein 4, abdominal fat mass, peak bone mineral density, and markers of bone metabolism in men: The northern osteoporosis and obesity (NO2) study. Eur J Endocrinol. 158:765–770. 2008. View Article : Google Scholar : PubMed/NCBI
164	He H, Zhang Y, Sun Y, Zhang Y, Xu J, Yang Y and Chen J: Folic acid attenuates high-fat diet-induced osteoporosis through the AMPK signaling pathway. Front Cell Dev Biol. 9:7918802022. View Article : Google Scholar : PubMed/NCBI
165	Fu L, Wang Y and Hu YQ: Causal effects of B vitamins and homocysteine on obesity and musculoskeletal diseases: A Mendelian randomization study. Front Nutr. 9:10481222022. View Article : Google Scholar : PubMed/NCBI
166	Jeon S, Lee J, Shin Y and Yoon M: Ascorbic acid reduces insulin resistance and pancreatic steatosis by regulating adipocyte hypertrophy in obese ovariectomized mice. Can J Physiol Pharmacol. 101:294–303. 2023. View Article : Google Scholar
167	Rahman F, Bordignon B, Culerrier R, Peiretti F, Spicuglia S, Djabali M, Landrier JF and Fontes M: Ascorbic acid drives the differentiation of mesoderm-derived embryonic stem cells. Involvement of p38 MAPK/CREB and SVCT2 transporter. Mol Nutr Food Res. 61:16005062017. View Article : Google Scholar
168	Alzahrani BA, Badri ZA, Aljuhani JA, Alshamrani RM, Ahmed ME and Jari Alshumrani M: A comparison of magnesium levels in obese versus normal-weight children. Cureus. 15:e440532023.PubMed/NCBI
169	Li J, Gao Y, Yu T, Lange JK, LeBoff MS, Gorska A, Luu S, Zhou S and Glowacki J: Obesity and leptin influence vitamin D metabolism and action in human marrow stromal cells. J Steroid Biochem Mol Biol. 198:1055642020. View Article : Google Scholar
170	Xu SM, Lu K, Yang XF, Ye YW, Xu MZ, Shi Q, Gong YQ and Li C: Association of 25-hydroxyvitamin D levels with lipid profiles in osteoporosis patients: A retrospective cross-sectional study. J Orthop Surg Res. 18:5972023. View Article : Google Scholar
171	Chin KY, Pang KL and Soelaiman IN: Tocotrienol and its role in chronic diseases. Adv Exp Med Biol. 928:97–130. 2016. View Article : Google Scholar : PubMed/NCBI
172	Ima-Nirwana S and Suhaniza S: Effects of tocopherols and tocotrienols on body composition and bone calcium content in adrenalectomized rats replaced with dexamethasone. J Med Food. 7:45–51. 2004. View Article : Google Scholar
173	Ilich JZ: Osteosarcopenic adiposity syndrome update and the role of associated minerals and vitamins. Proc Nutr Soc. 80:344–355. 2021. View Article : Google Scholar : PubMed/NCBI
174	Kim M, Na W and Sohn C: Vitamin K1 (phylloquinone) and K2 (menaquinone-4) supplementation improves bone formation in a high-fat diet-induced obese mice. J Clin Biochem Nutr. 53:108–113. 2013. View Article : Google Scholar : PubMed/NCBI
175	Shi HY, Yan SM, Guo YM, Zhang BQ, Guo XY and Shi BL: Vitamin A pretreatment protects NO-induced bovine mammary epithelial cells from oxidative stress by modulating Nrf2 and NF-κB signaling pathways. J Anim Sci. 96:1305–1316. 2018. View Article : Google Scholar :
176	Jiang WD, Zhang L, Feng L, Wu P, Liu Y, Kuang SY, Li SW, Tang L, Mi HF, Zhang L and Zhou XQ: New insight on the immune modulation and physical barrier protection caused by vitamin A in fish gills infected with flavobacterium columnare. Front Immunol. 13:8334552022. View Article : Google Scholar :
177	Behr GA, Schnorr CE and Moreira JCF: Increased blood oxidative stress in experimental menopause rat model: The effects of vitamin A low-dose supplementation upon antioxidant status in bilateral ovariectomized rats. Fundam Clin Pharmacol. 26:235–249. 2012. View Article : Google Scholar
178	Xu LL, Zhao B, Sun SL, Yu SF, Wang YM, Ji R, Yang ZT, Ma L, Yao Y, Chen Y, et al: High-dose vitamin C alleviates pancreatic injury via the NRF2/NQO1/HO-1 pathway in a rat model of severe acute pancreatitis. Ann Transl Med. 8:8522020. View Article : Google Scholar :
179	Ulas M and Cay M: 17β-Estradiol and vitamin E modulates oxidative stress-induced kidney toxicity in diabetic ovariectomized rat. Biol Trace Elem Res. 144:821–831. 2011. View Article : Google Scholar
180	Farshbaf-Khalili A, Ostadrahimi A, Mirghafourvand M, Ataei-Almanghadim K, Dousti S and Iranshahi AM: Clinical efficacy of curcumin and vitamin E on inflammatory-oxidative stress biomarkers and primary symptoms of menopause in healthy postmenopausal women: A triple-blind randomized controlled trial. J Nutr Metab. 2022:63397152022. View Article : Google Scholar :
181	Liu J, Tang Y, Peng B, Tian C and Geng B: Bone mineral density is associated with composite dietary antioxidant index among US adults: Results from NHANES. Osteoporos Int. 34:2101–2110. 2023. View Article : Google Scholar
182	Zhou Q, Chen X, Chen Q and Hao L: Independent and combined associations of dietary antioxidant intake with bone mineral density and risk of osteoporosis among elderly population in United States. J Orthop Sci. 29:1064–1072. 2024. View Article : Google Scholar
183	Arnold M, Rajagukguk YV and Gramza-Michałowska A: Functional food for elderly high in antioxidant and chicken eggshell calcium to reduce the risk of osteoporosis-A narrative review. Foods. 10:6562021. View Article : Google Scholar
184	Zhou P, Shao R, Wang H, Miao J and Wang X: Dietary vitamin A, C, and E intake and subsequent fracture risk at various sites: A meta-analysis of prospective cohort studies. Medicine (Baltimore). 99:e208412020. View Article : Google Scholar
185	Zinnuroglu M, Dincel AS, Kosova F, Sepici V and Karatas GK: Prospective evaluation of free radicals and antioxidant activity following 6-month risedronate treatment in patients with postmenopausal osteoporosis. Rheumatol Int. 32:875–880. 2012. View Article : Google Scholar
186	Scioli MG, Coniglione F, Greggi C, Evangelista L, Fiorelli E, Savino L, Ferlosio A, Piccirilli E, Gasbarra E, Iundusi R, et al: Ascorbic acid reduces Ropivacaine-induced myotoxicity in cultured human osteoporotic skeletal muscle cells. BMC Musculoskelet Disord. 24:5762023. View Article : Google Scholar : PubMed/NCBI
187	Deyhim F, Strong K, Deyhim N, Vandyousefi S, Stamatikos A and Faraji B: Vitamin C reverses bone loss in an osteopenic rat model of osteoporosis. Int J Vitam Nutr Res. 88:58–64. 2018. View Article : Google Scholar
188	Nojiri H, Saita Y, Morikawa D, Kobayashi K, Tsuda C, Miyazaki T, Saito M, Marumo K, Yonezawa I, Kaneko K, et al: Cytoplasmic superoxide causes bone fragility owing to low-turnover osteoporosis and impaired collagen cross-linking. J Bone Miner Res. 26:2682–2694. 2011. View Article : Google Scholar
189	Sangani R, Naime M, Zakhary I, Ahmad S, Chutkan N, Zhu A, Ha Y, Hamrick M, Isales C, Elsalanty M, et al: Regulation of vitamin C transporter in the type 1 diabetic mouse bone and bone marrow. Exp Mol Pathol. 95:298–306. 2013. View Article : Google Scholar : PubMed/NCBI
190	Fulzele S, Chothe P, Sangani R, Chutkan N, Hamrick M, Bhattacharyya M, Prasad PD, Zakhary I, Bowser M, Isales C and Ganapathy VC: Sodium-dependent vitamin C transporter SVCT2: Expression and function in bone marrow stromal cells and in osteogenesis. Stem Cell Res. 10:36–47. 2013. View Article : Google Scholar
191	Massaccesi L, Ragone V, Papini N, Goi G, Corsi Romanelli MM and Galliera E: Effects of vitamin E-stabilized ultra high molecular weight polyethylene on oxidative stress response and osteoimmunological response in human osteoblast. Front Endocrinol (Lausanne). 10:2032019. View Article : Google Scholar : PubMed/NCBI
192	Casado-Díaz A, Túnez-Fiñana I, Mata-Granados JM, Ruiz-Méndez MV, Dorado G, Romero-Sánchez MC, Navarro-Valverde C and Quesada-Gómez JM: Serum from postmenopausal women treated with a by-product of olive-oil extraction process stimulates osteoblastogenesis and inhibits adipogenesis in human mesenchymal stem-cells (MSC). Exp Gerontol. 90:71–78. 2017. View Article : Google Scholar : PubMed/NCBI
193	Casati L, Pagani F, Limonta P, Vanetti C, Stancari G and Sibilia V: Beneficial effects of δ-tocotrienol against oxidative stress in osteoblastic cells: Studies on the mechanisms of action. Eur J Nutr. 59:1975–1987. 2020. View Article : Google Scholar
194	Quigley M, Rieger S, Capobianco E, Wang Z, Zhao H, Hewison M and Lisse TS: Vitamin D modulation of mitochondrial oxidative metabolism and mTOR enforces stress adaptations and anticancer responses. JBMR Plus. 6:e105722021. View Article : Google Scholar
195	Yüksek V, Dede S, Çetin S, Usta A and Taşpınar M: Vitamin D may assist the UPR against sodium fluoride-induced damage by reducing RIPK1, ATG5, BECN1, oxidative stress and increasing caspase-3 in the osteoblast MC3T3-E1 cell line. J Trace Elem Med Biol. 80:1272932023. View Article : Google Scholar : PubMed/NCBI
196	Xu P, Lin B, Deng X, Huang K, Zhang Y and Wang N: VDR activation attenuates osteoblastic ferroptosis and senescence by stimulating the Nrf2/GPX4 pathway in age-related osteoporosis. Free Radic Biol Med. 193:720–735. 2022. View Article : Google Scholar
197	Ma Q, Liang M, Tang X, Luo F and Dou C: Vitamin B5 inhibit RANKL induced osteoclastogenesis and ovariectomy induced osteoporosis by scavenging ROS generation. Am J Transl Res. 11:5008–5018. 2019.
198	Bădilă AE, Rădulescu DM, Ilie A, Niculescu AG, Grumezescu AM and Rădulescu AR: Bone regeneration and oxidative stress: An updated overview. Antioxidants (Basel). 11:3182022. View Article : Google Scholar
199	Cui Y, Zhang W, Yang P, Zhu S, Luo S and Li M: Menaquinone-4 prevents medication-related osteonecrosis of the jaw through the SIRT1 signaling-mediated inhibition of cellular metabolic stresses-induced osteoblast apoptosis. Free Radic Biol Med. 206:33–49. 2023. View Article : Google Scholar : PubMed/NCBI
200	Torres HM, Arnold KM, Oviedo M, Westendorf JJ and Weaver SR: Inflammatory processes affecting bone health and repair. Curr Osteoporos Rep. 21:842–853. 2023. View Article : Google Scholar
201	Moazen M, Mazloom Z, Tanideh N, Dabbaghmanesh MH, Rahmdel S, Azarpira N and Fararouei M: Osteoprotective effects of kefir fortified with omega-3 and vitamin C in ovariectomized rats. Int J Vitam Nutr Res. 93:200–209. 2023. View Article : Google Scholar
202	Shevchuk S, Marynych L, Malovana T and Denyshchych L: Vitamin D level in patients with systemic lupus erythematosus: Its relationship to disease course and bone mineral density. Lupus Sci Med. 10:e0009682023. View Article : Google Scholar : PubMed/NCBI
203	Shen CL, Mo H, Dunn DM and Watkins BA: Tocotrienol Supplementation led to higher serum levels of lysophospholipids but lower acylcarnitines in postmenopausal women: A randomized double-blinded placebo-controlled clinical trial. Front Nutr. 8:7667112021. View Article : Google Scholar
204	Liang G, Kow ASF, Tham CL, Ho YC and Lee MT: Ameliorative effect of tocotrienols on perimenopausal-associated osteoporosis-A review. Antioxidants (Basel). 11:21792022. View Article : Google Scholar : PubMed/NCBI
205	Nazrun Shuid A, Das S and Mohamed IN: Therapeutic effect of vitamin E in preventing bone loss: An evidence-based review. Int J Vitam Nutr Res. 89:357–370. 2019. View Article : Google Scholar
206	Jadhav N, Ajgaonkar S, Saha P, Gurav P, Pandey A, Basudkar V, Gada Y, Panda S, Jadhav S, Mehta D and Nair S: Molecular pathways and roles for vitamin K2-7 as a health-beneficial nutraceutical: Challenges and opportunities. Front Pharmacol. 13:8969202022. View Article : Google Scholar
207	Myneni VD and Mezey E: Immunomodulatory effect of vitamin K2: Implications for bone health. Oral Dis. 24:67–71. 2018. View Article : Google Scholar : PubMed/NCBI
208	Guo L, Zhang Y, Liu H, Cheng Q, Yang S and Yang D: All-trans retinoic acid inhibits the osteogenesis of periodontal ligament stem cells by promoting IL-1β production via NF-κB signaling. Int Immunopharmacol. 108:1087572022. View Article : Google Scholar
209	Ahmed N, Sammons J, Khokher MA and Hassan HT: Retinoic acid suppresses interleukin 6 production in normal human osteoblasts. Cytokine. 12:289–293. 2000. View Article : Google Scholar : PubMed/NCBI
210	Yang K, Wang X, Zhang C, Liu D and Tao L: Metformin improves HPRT1-targeted purine metabolism and repairs NR4A1-mediated autophagic flux by modulating FoxO1 nucleocytoplasmic shuttling to treat postmenopausal osteoporosis. Cell Death Dis. 15:7952024. View Article : Google Scholar : PubMed/NCBI
211	Li Y, Hou B, Zhang Y, Wang Y, Chu Y and Li X: In vivo quantitative assessment of proximal femoral cortical bone microstructure using double-echo ultrashort echo time magnetic resonance imaging. Quant Imaging Med Surg. 14:9323–9334. 2024. View Article : Google Scholar : PubMed/NCBI
212	McClung MR: Sequential and long-term therapy for osteoporosis. Curr Osteoporos Rep. 23:152025. View Article : Google Scholar
213	Li P, Zhu Z, Wang Y, Zhang X, Yang C, Zhu Y, Zhou Z, Chao Y, Long Y, Gao Y, et al: Substrate transport and drug interaction of human thiamine transporters SLC19A2/A3. Nat Commun. 15:109242024. View Article : Google Scholar
214	Mydlárová Blaščáková M, Lőrinczová Z, Anderková L, Czerwińska-Ledwig O, Mikulová Ľ, Hrušovská H, Jędrzejkiewicz B and Piotrowska A: Relationship between vitamin D Receptor gene bsmi polymorphism and 25-hydroxyvitamin D total levels in slovak postmenopausal women with reduced bone mineral density. Genes (Basel). 16:3372025. View Article : Google Scholar
215	Wu Z, Ye Q, Zhang S, Hu LP, Wang XQ, Yao LL, Zhu L, Xiao SY, Duan ZH, Zhang XL, et al: Vitamin K-dependent gamma-carboxyglutamic acid protein 1 promotes pancreatic ductal adenocarcinoma progression through stabilizing oncoprotein KRAS and tyrosine kinase receptor EGFR. Clin Transl Med. 15:e701912025. View Article : Google Scholar : PubMed/NCBI
216	Rupp T, Butscheidt S, Vettorazzi E, Oheim R, Barvencik F, Amling M and Rolvien T: High FGF23 levels are associated with impaired trabecular bone microarchitecture in patients with osteoporosis. Osteoporos Int. 30:1655–1662. 2019. View Article : Google Scholar
217	Cui A, Xiao P, Fan Z, Zeng Y, Wang H and Zhuang Y: Associations between vitamin E status and bone mineral density in children and adolescents aged 8-19 years: Evidence based on NHANES 2005-2006, 2017-2018. PLoS One. 18:e02831272023. View Article : Google Scholar
218	Orhadje E, Berg K, Hauser B and Ralston SH: Clinical features, incidence and treatment outcome in pregnancy-associated osteoporosis: A single-centre experience over two decades. Calcif Tissue Int. 113:591–596. 2023. View Article : Google Scholar :
219	Li H, Wang C, Jin Y, Cai Y, Sun H and Liu M: The integrative analysis of competitive endogenous RNA regulatory networks in osteoporosis. Sci Rep. 12:95492022. View Article : Google Scholar :
220	Li S, Liu F, Zheng K, Wang W, Qiu E, Pei Y, Wang S, Zhang J and Zhang X: CircDOCK1 promotes the tumorigenesis and cisplatin resistance of osteogenic sarcoma via the miR-339-3p/IGF1R axis. Mol Cancer. 20:1612021. View Article : Google Scholar
221	Guan Y, Zhang W, Mao Y and Li S: Nanoparticles and bone microenvironment: A comprehensive review for malignant bone tumor diagnosis and treatment. Mol Cancer. 23:2462024. View Article : Google Scholar :
222	Zhu X and Li S: Nanomaterials in tumor immunotherapy: New strategies and challenges. Mol Cancer. 22:942023. View Article : Google Scholar
223	Chen Z, Yue Z, Yang K and Li S: Nanomaterials: Small particles show huge possibilities for cancer immunotherapy. J Nanobiotechnology. 20:4842022. View Article : Google Scholar : PubMed/NCBI

July-2025
Volume 56 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

Recommend to Library

Journal Metrics
Impact Factor: 5.7
Ranked Medicine Research and Experimental
(total number of cites)
CiteScore: 13.2
CiteScore Rank: Q1: #23/348 Biochemistry, Genetics and Molecular Biology
Source Normalized Impact per Paper (SNIP): 1.28
SCImago Journal Rank (SJR): 1.381

Vitamins	Role in women's health	Effects on bone tissue	Mechanism
Vitamin A	Associated with the risk of estrogen receptor-tumors	Increasing the occurrence offractures	-
Vitamin B9	-	Decreasing asymptomatic osteoporotic vertebral fractures	Increasing osteocalcin and β-CrossLaps levels
Vitamin B12	-	Preventing osteoporosis in postmenopausal women	-
Vitamin C	Promoting the secretion of gonads and increasing the concentration of estrogen	Associated with hip BMD	Improving the abnormal state between bones, muscles and adipose tissue
Vitamin D	Delaying menopause and extending reproductive lifespan, associated with the healthy index of postmenopausal women	Elevating bone quality and strength	An important bone turnover marker, improving irisin levels to enhance skeletal muscle strength and increase bone mass
Vitamin E	Promoting the secretion of estrogen and improving menopausal complications	Improving bone mineral content and reconstructing bone microstructure	Inhibiting the expression of sclerostin and decreasing the RANKL/OPG ratio
Vitamin K	-	Promoting osteogenic differentiation and matrix mineralization	Increasing the expression of Runx2 and BMP2, but decreasing NFATC1 and CTSK expression

Viatmins	Role in obesity	Effects on bone tissue	Mechanism
Vitamin A	Increasing the efficiency of fat burning	Inhibiting bone loss and destruction	Related to osteocalcin concentration
Vitamin B2	Regulating the synthesis, decomposition and secretion of fat, lowering body fat levels	Preventing bone loss	-
Vitamin B9	-	Attenuating HFD-induced osteoporosis	Increasing the expression of Nrf2 and antioxidant enzymes, activating the AMPK signaling pathway
Vitamin B12	Negatively correlated with body fat	-	-
Vitamin C	-	Preventing the occurrence of obesity-associated osteoporosis	Propelling the differentiation direction of MSCs toward osteogenesis rather than adipogenesis
Vitamin D	Negatively correlated with blood triglyceride concentration but positively correlated with apolipoprotein A, lipoprotein A and high-density lipoprotein cholesterol	-	-
Vitamin E	Inhibiting the synthesis of cholesterol to treat hyperlipidemia	Enhancing bone quality	-
Vitamin K	-	Preventing HFD- induced bone loss	Promoting osteocalcin-mediated bone formation and inhibiting RANKL-induced bone resorption

International Journal
of Molecular
Medicine