The vitamin D receptor (VDR), a member of the nuclear receptor superfamily of transcriptional regulators, is crucial to calcitriol signalling. VDR is regulated by genetic and environmental factors and it is hypothesised that the response to vitamin D supplementation could be modulated by genetic variants in the VDR gene. The best studied polymorphisms in the VDR gene are Apal (rs7975232), BsmI (rs1544410), Taql (rs731236) and Fokl (rs10735810). We conducted a systematic review and meta-analysis to evaluate the response to vitamin D supplementation according to the BsmI, TaqI, ApaI and FokI polymorphisms. We included studies that analysed the relationship between the response to vitamin D supplementation and the genotypic distribution of these polymorphisms. We included eight studies that enrolled 1038 subjects. The results showed no significant association with the BsmI and ApaI polymorphisms (p = 0.081 and p = 0.63) and that the variant allele (Tt+tt) of the TaqI polymorphism and the FF genotype of the FokI variant were associated with a better response to vitamin D supplementation (p = 0.02 and p < 0.001). In conclusion, the TaqI and FokI polymorphisms could play a role in the modulation of the response to vitamin D supplementation, as they are associated with a better response to supplementation.

Bone is crucial for the support of muscles and the protection of vital organs, and as a reservoir of calcium and phosphorus. Bone is one of the most metabolically active tissues and is continuously renewed to adapt to the changes required for healthy functioning. To maintain normal cellular and physiological bone functions sufficient oxygen is required, as evidence has shown that hypoxia may influence bone health. In this scenario, this review aimed to analyze the molecular mechanisms involved in hypoxia-induced bone remodeling alterations and their possible clinical consequences. Hypoxia has been associated with reduced bone formation and reduced osteoblast matrix mineralization due to the hypoxia environment inhibiting osteoblast differentiation. A hypoxic environment is involved with increased osteoclastogenesis and increased bone resorptive capacity of the osteoclasts. Clinical studies, although with contradictory results, have shown that hypoxia can modify bone remodeling.

Background and aims: The relationship between obesity and bone metabolism is controversial. In recent decades, the protective role of obesity in the development of osteoporosis is questioned. The aims of this study are the following: to evaluate the differences in bone turnover markers between postmenopausal women with and without obesity and to compare the risk of fracture at five years between these groups. Methods: An observational longitudinal prospective cohort study of postmenopausal women with obesity (O) (body mass index (BMI) > 30 kg/m²) and non-obesity (NoO) (BMI < 30 kg/m²) is designed. 250 postmenopausal women are included in the study (NoO: 124 (49.6%) and O: 126 (50.4%)). It measures epidemiological variables, dietary variables (calcium intake, vitamin D intake, smoking, alcohol consumption, and physical activity), biochemicals (β-crosslap, type I procollagen amino-terminal peptide (P1NP), 25OH-vitamin D, and parathyroid hormone (PTH)), anthropometric variables, and fracture data five years after the start of the study. The mean age is 56.17 (3.91) years. Women with obesity showed lower levels of vitamin D (O: 17.27 (7.85) ng/mL, NoO: 24.51 (9.60) ng/mL; p < 0.01), and higher levels of PTH (O: 53.24 (38.44–65.96) pg/mL, NoO: 35.24 (25.36–42.40) pg/mL; p < 0.01). Regarding the bone formation marker (P1NP), it was found to be high in women without obesity, O: 45.46 (34.39–55.16) ng/mL, NoO: 56.74 (45.34–70.74) ng/mL; p < 0.01; the bone resorption marker (β-crosslap) was found to be high in women with obesity, being significant in those older than 59 years (O: 0.39 (0.14) ng/mL, NoO 0.24 (0.09) ng/mL; p < 0.05). No differences are observed in the risk of fracture at 5 years based on BMI (OR = 0.90 (95%CI 0.30–2.72); p = 0.85). Conclusions: Postmenopausal women with obesity showed lower levels of bone formation markers; older women with obesity showed higher markers of bone resorption.

Calcifediol (25-OH-vitamin D3) is the prohormone of the vitamin D endocrine system. It is used to prevent and treat vitamin D deficiency. Calcifediol, as well as cholecalciferol (vitamin D3), is efficient and safe in the general population, although calcifediol has certain advantages over cholecalciferol, such as its rapid onset of action and greater potency. This review analyzed studies comparing the efficacy and safety of both calcifediol and cholecalciferol drugs in the short and long term (>6 months). Calcifediol was found to be more efficacious, with no increase in toxicity. We also assessed the predictability of both molecules. A 25OHD increase depends on the dose and frequency of calcifediol administration. In contrast, after cholecalciferol administration, 25OHD increase depends on more factors than dose and frequency of administration, also phenotypic aspects (such as obesity and malabsorption), and genotypic factors impacts in this increase.

Background: Insulin may play a key role in bone metabolism, where the anabolic effect predominates. This study aims to analyze the relationship between insulin resistance and bone quality using the trabecular bone score (TBS) and three-dimensional dual-energy X-ray absorptiometry (3D-DXA) in non-diabetic postmenopausal women by determining cortical and trabecular compartments. Methods: A cross-sectional study was conducted in non-diabetic postmenopausal women with suspected or diagnosed osteoporosis. The inclusion criteria were no menstruation for more than 12 months and low bone mass or osteoporosis as defined by DXA. Glucose was calculated using a Hitachi 917 auto-analyzer. Insulin was determined using an enzyme-linked immunosorbent assay (EIA). Insulin resistance was estimated using a homeostasis model assessment of insulin resistance (HOMA-IR). DXA, 3D-DXA, and TBS were thus collected. Moreover, we examined bone parameters according to quartile of insulin, hemoglobin A1C (HbA1c), and HOMA-IR. Results: In this study, we included 381 postmenopausal women. Women located in quartile 4 (Q4) of HOMA-IR had higher values of volumetric bone mineral density (vBMD) but not TBS. The increase was higher in the trabecular compartment (16.4%) than in the cortical compartment (6.4%). Similar results were obtained for insulin. Analysis of the quartiles by HbA1c showed no differences in densitometry values, however women in Q4 had lower levels of TBS. After adjusting for BMI, statistical significance was maintained for TBS, insulin, HOMA-IR, and HbA1c. Conclusions: In non-diabetic postmenopausal women there was a direct relationship between insulin resistance and vBMD, whose effect is directly related to greater weight. TBS had an inverse relationship with HbA1c, insulin, and insulin resistance unrelated to weight. This might be explained by the formation of advanced glycosylation products (AGEs) in the bone matrix, which reduces bone deformation capacity and resistance, as well as increases fragility.