Excess body weight due to obesity has traditionally been considered to have a positive effect on bone; however, more recent findings suggest that bone quality is compromised. Both obesity and caloric restriction increase fracture risk and are regulated by endocrine factors and cytokines that have direct and indirect effects on bone and calcium absorption. Weight reduction will decrease bone mass and mineral density, but this varies by the individual’s age, gender, and adiposity. Dietary modifications, exercise, and medications have been shown to attenuate the bone loss associated with weight reduction. Future obesity and weight loss trials would benefit from assessment of key hormones, adipokine and gut peptides that regulate calcium absorption, and bone mineral density and quality by using sensitive techniques in high-risk populations.

Weight reduction induces bone loss by several factors, and the effect of higher protein (HP) intake during caloric restriction on bone mineral density (BMD) is not known. Previous study designs examining the longer-term effects of HP diets have not controlled for total calcium intake between groups and have not examined the relationship between bone and endocrine changes. In this randomized, controlled study, we examined how BMD (areal and volumetric), turnover markers, and hormones [insulin-like growth factor 1 (IGF-1), IGF-binding protein 3 (IGFBP-3), 25-hydroxyvitamin D, parathyroid hormone (PTH), and estradiol] respond to caloric restriction during a 1-year trial using two levels of protein intake. Forty-seven postmenopausal women (58.0 AE 4.4 years; body mass index of 32.1 AE 4.6 kg/ m 2 ) completed the 1-year weight-loss trial and were on a higher (HP, 24%, n ¼ 26) or normal protein (NP, 18%, n ¼ 21) and fat intake (28%) with controlled calcium intake of 1.2 g/d. After 1 year, subjects lost 7.0% AE 4.5% of body weight, and protein intake was 86 and 60 g/d in the HP and NP groups, respectively. HP compared with NP diet attenuated loss of BMD at the ultradistal radius, lumbar spine, and total hip and trabecular volumetric BMD and bone mineral content of the tibia. This is consistent with the higher final values of IGF-1 and IGFBP-3 and lower bone-resorption marker (deoxypyridinoline) in the HP group than in the NP group ( p < .05). These data show that a higher dietary protein during weight reduction increases serum IGF-1 and attenuates total and trabecular bone loss at certain sites in postmenopausal women. ß

Summary The goal in this study was to determine the relationship between body mass index and trabecular and cortical bone using quantitative computed tomography. A higher body mass index (BMI) was positively associated with trabecular and cortical bone parameters, and serum parathyroid hormone, and negatively associated with cortical volumetric bone mineral density (vBMD) and serum 25-hydroxy-vitamin D. When BMI is greater than 35 kg/m2, adiposity affects vBMD and may explain the higher fracture risk in this population without low BMD. Introduction The influence of adult obesity on the trabecular and cortical bone, geometry, and strength has not been fully addressed. The goal in this study was to determine the relationship between body mass index and trabecular and cortical bone mass and geometry, over a wide range of body weights. Methods We examined 211 women (25–71 years; BMI 18–57 kg/m2) who were classified into three categories of BMI (kg/m2) including normal-weight (BMI<25), overweight and obese-class I (BMI 25–35) and obese-class II–III (BMI>35), and also by menopausal status. Volumetric bone mineral density (mg/cm3), trabecular, and cortical components as well as geometric characteristics at the 4%, 38%, and 66% from the distal tibia were measured by peripheral quantitative computed tomography, and serum was analyzed for parathyroid hormone (PTH) and 25-hydroxy-vitamin D (25OHD). Results Higher BMI was associated with greater values of trabecular bone and cortical BMC and area and PTH (r>0.39, p<0.001), but lower cortical vBMD and 25OHD (r>−0.27, p<0.001). When controlling for lower leg muscle area, fat area was inversely associated with cortical vBMD (r=−0.16, p<0.05). Premenopausal obese women with both higher BMI and PTH had lower cortical vBMD (r<−0.40, p<0.001). While age is a predictor for most bone variables, fat mass explains more variance for vBMD, and lean mass and 25OHD explain greater variance in geometric and strength indices (p<0.05). Conclusions Severe obesity (BMI>35) increases trabecular vBMD and in the presence of a higher PTH is associated with a lower cortical vBMD without compromising bone geometry and strength. Whether or not a lower cortical vBMD in obesity influences fracture risk over time needs to be further explored.

The decline in Ct thickness was prevented with higher vitamin D supplementation, but there were no other significant changes due to treatment over 1 year. Whether these findings translate to changes in biomechanical properties leading to reduced fracture risk should be addressed in future studies.

These data show that vitamin D supplementation increases TFCA and that WL decreases TFCA and suggest that, when calcium intake is 1.2 g/d, either 10 or 63 μg vitamin D/d is sufficient to maintain the calcium balance. This trial was registered at clinicaltrials.gov as NCT00473031.

Obesity is often associated with vitamin D deficiency and secondary hyperparathyroidism. Vitamin D supplementation typically leads to the reductions in serum parathyroid hormone (PTH) levels, as shown in normal weight individuals. Meanwhile, the dose of vitamin D supplementation for the suppression of PTH may differ in overweight and obese adults. We conducted a systematic review and meta-analysis of randomized controlled trials to determine the dose of vitamin D supplementation required to suppress PTH levels in overweight/obese individuals. We identified 18 studies that examined overweight or obese healthy adults who were supplemented with varying doses of vitamin D3. The primary outcomes examined were changes in PTH and serum 25-hydroxyvitamin D (25OHD) levels from baseline to post-treatment. The results of the meta-analysis showed that there was a significant treatment effect of vitamin D supplementation on PTH, total standardized mean difference (SMD) (random effects) = −0.38 (95% CI = −0.56 to −0.20), t = −4.08, p < 0.001. A significant treatment effect of vitamin D supplementation was also found on 25OHD, total SMD (random effects) = 2.27 (95% CI = 1.48 to 3.06) t = 5.62, p < 0.001. Data from available clinical trials that supplemented adults with D3 ranging from 400 IU to 5714 IU, showed that 1000 IU of vitamin D supplementation best suppressed serum PTH levels, total SMD = −0.58, while vitamin D supplementation with 4000 IU showed the greatest increase in serum 25OH levels. Vitamin D and calcium supplementation of 700 IU and 500 mg, respectively, also showed a significant treatment effect on the suppression of PTH with a total SMD = −5.30 (95% CI = −9.72 to −0.88). In conclusion, the meta analysis of available clinical trials indicates that 1000 IU vitamin D supplementation can suppress serum PTH levels, while 4000 IU of vitamin D was associated with the largest increase in serum 25OHD levels in the overweight and obese population.

Vitamin D may affect cognitive performance, but previous studies are either short term or observational. We conducted a randomized controlled trial of vitamin D supplementation on domain-specific cognitive measures in postmenopausal women. Overweight/obese women with serum 25-hydroxyvitamin D (25OHD) levels less than 30 ng/mL were recruited. Vitamin D3 supplementation (600, 2,000, or 4,000 IU/d) was randomly assigned in a double-blinded manner for 1 year. Serum 25-hydroxyvitamin D, osteocalcin (total and undercarboxylated), amyloid beta, parathyroid hormone, and estradiol were analyzed before and after supplementation. Cognitive tests were administered after treatment. The women (58 ± 6 years; body mass index, 30.0 ± 3.5 kg/m2) had a baseline serum 25-hydroxyvitamin D level of 22.6 ± 5.8 ng/mL that increased to 30.2 ± 5.6, 36.0 ± 4.9, and 40.8 ± 7.0 ng/mL in the 600, 2,000, and 4,000 IU/d groups, respectively (p &lt; .001). Participants taking 2,000 IU/d compared to other doses performed better in learning and memory tests (p &lt; .05), yet the 4,000 IU/d group had a slower reaction time compared to the 600 IU/d group. Multiple regression indicated that serum undercarboxylated osteocalcin predicted tasks associated with reaction time and executive function, whereas body mass index and parathyroid hormone negatively predicted reaction time and executive function (p ≤ .01). These data suggest that vitamin D has differential effects on domain-specific cognitive measures and that a higher dose may negatively affect reaction time.

Objective Short-term weight loss is accompanied by bone loss in postmenopausal women. The longer-term impact on bone in the reduced overweight/obese woman compared to those who regain their weight was examined in this study using a case-control design. Methods Postmenopausal women (n = 42, body mass index of 28.3 ± 2.8 kg/m2; 60.7 ± 5.5 y) were recruited 2 years after the start of a 6 month weight loss trial and those who maintained their weight (WL-M) were matched to a cohort who regained weight (WL-R). Serum hormones and bone markers were measured in a subset. Bone mineral density (BMD) at the femoral neck (FN), trochanter, spine, radius, and total body and soft tissue composition were taken at baseline, 0.5 and 2 years. Results During WL, both groups lost 9.3 ± 3.4% body weight with no significant difference between groups. After weight loss, weight change was −0.1 ± 2.7 % and 6.0 ± 3.3% in the WL-M (n=22) and WL-R (n=20) groups, respectively. After 2 years, both groups lost BMD at the FN and trochanter (p ≤ 0.01), whereas only the WL-M group reduced BMD at the 1/3 radius (p < 0.001). There was a greater BMD loss at the trochanter (−6.8 ± 5.7%) and the 1/3 radius (−4.5 ± 3.3%) in the WL-M compared to the WL-R group after 2 years. Multiple linear regression showed that change in leg fat mass (but not trunk fat) contributed to trochanter BMD loss (p <0.05). Conclusions After 2 years, there is no BMD recovery of weight reduction-induced bone loss, irrespective of weight-regain. These data suggest that the period after weight loss may be an important point in time to prevent bone loss for both those who maintain or regain weight.