Changes in Bone Mineral Density During and After Lactation in Ugandan Women With HIV on Tenofovir-Based Antiretroviral Therapy

Antiretroviral therapy (ART) in people living with human immunodeficiency virus (HIV) is associated with bone loss, but data are limited in lactation, when physiological bone mineral mobilization is occurring. This research charted changes in areal bone mineral density (aBMD) during and after lactation in Ugandan women with HIV (WWH) initiated onto ART in pregnancy, compared to women without HIV (REF). One-hundred WWH on tenofovir-based ART and 100 REF were enrolled in pregnancy. Lumbar spine (LS), total hip (TH), and whole-body-less-head (WBLH) aBMD were measured by dual-energy X-ray absorptiometry (DXA) at 2, 14, and 26 weeks of lactation, and at 3 months postlactation. The primary outcome was the difference between groups in mean percent change in LS aBMD between 2 and 14 weeks. Statistical analysis was performed in hierarchical repeated measures ANOVA models that corrected for multiple testing. Median age was 23.4 (IQR, 21.0 to 26.8) years. WWH had lower body weight. aBMD decreased in both groups during lactation, but WWH had greater decreases at TH (2-to-26 weeks: WWH [n = 63] −5.9% [95% CI, −6.4 to −5.4] versus REF [n = 64] −4.3% [95% CI, −4.8 to −3.8]; group*time point interaction p = .008). Decreases in LS aBMD were similar in WWH and REF (2-to-26 weeks: −2.0% [95% CI, −2.5 to −1.5]), although there was a tendency toward a smaller decrease in WWH between 2 and 14 weeks (WWH [n = 77] −1.8% [95% CI, −2.2 to −1.4] versus REF [n = 69] −2.9% [95% CI, −3.3 to −2.5]; group*time point interaction p = .08). Postlactation, LS aBMD was higher relative to week 2 in both groups. TH and WBLH aBMD did not return to week 2 values in WWH but did in REF (TH postlactation versus week 2: WWH [n = 61] −3.1% [95% CI, −3.6 to −2.6]; REF [n = 29] +0.1% [95% CI, −0.9 to +1.1]). These data show accentuated bone loss during lactation and only partial skeletal recovery by 3 months postlactation in Ugandan WWH on tenofovir-based ART. Studies are ongoing to understand longer-term consequences for bone health. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.     

Vitamin D Supplementation After Parathyroidectomy: Effect on Bone Mineral Density—A Randomized Double‐Blind Study

Patients with primary hyperparathyroidism (PHPT) have higher bone turnover, lower bone mineral density (BMD), and an increased risk of fractures. They also have a high incidence of low vitamin D levels (25‐OH‐vitamin D <50 nmol/L) that could worsen the negative effect on the bone. In this double‐blinded clinical trial, 150 patients with PHPT were randomized, after successful parathyroidectomy (PTX), to 1‐year daily treatment with either cholecalciferol 1600 IU and calcium carbonate 1000 mg (D +) or calcium carbonate alone (D–). BMD was measured in the lumbar spine, femoral neck, total hip, distal and 33% radius using dual‐energy X‐ray absorptiometry (DXA) before surgery and after 1 year of study medication. Median age was 60 (range 30–80) years and there were 119 (79%) women and 31 (21%) men; 76% had 25‐OH‐D <50 nmol/L before PTX and 50% had persistent elevated parathyroid hormone (PTH) 6 weeks after PTX. A similar increase in BMD in the lumbar spine, femoral neck, and total hip was observed in both groups (D + : 3.6%, 3.2%, and 2.7%, p < 0.001, respectively; and D–: 3.0%, 2.3%, and 2.1%, respectively, p < 0.001). Patients with vitamin D supplementation also increased their BMD in distal radius (median 2.0%; interquartile range, ?1.7% to 5.4%; p = 0.013). The changes in BMD, especially in the hips, were correlated to the baseline concentrations of PTH, ionized calcium, and bone markers (p < 0.001). A benefit from vitamin D substitution was observed among patients with a persistent postoperative PTH elevation, who also improved their BMD at 33% radius and radius ultradistal (p < 0.05). In conclusion, except for a minor improvement of radius BMD, our data show no beneficial effect on BMD or bone turnover markers of vitamin D supplementation after PTX. Preoperative PTH seems to have the strongest association with improvement in BMD. © 2014 American Society for Bone and Mineral Research.     

Associations of 25‐Hydroxyvitamin D and 1,25‐Dihydroxyvitamin D With Bone Mineral Density,Bone Mineral Density Change,and Incident Nonvertebral Fracture

Relationships between 1,25‐dihydroxyvitamin D (1,25(OH)₂D) and skeletal outcomes are uncertain. We examined the associations of 1,25(OH)₂D with bone mineral density (BMD), BMD change, and incident non‐vertebral fractures in a cohort of older men and compared them with those of 25‐hydroxyvitamin D (25OHD). The study population included 1000 men (aged 74.6 ± 6.2 years) in the Osteoporotic Fractures in Men (MrOS) study, of which 537 men had longitudinal dual‐energy X‐ray absorptiometry (DXA) data (4.5 years of follow‐up). A case‐cohort design and Cox proportional hazards models were used to test the association between vitamin D metabolite levels and incident nonvertebral and hip fractures. Linear regression models were used to estimate the association between vitamin D measures and baseline BMD and BMD change. Interactions between 25OHD and 1,25(OH)₂D were tested for each outcome. Over an average follow‐up of 5.1 years, 432 men experienced incident nonvertebral fractures, including 81 hip fractures. Higher 25OHD was associated with higher baseline BMD, slower BMD loss, and lower hip fracture risk. Conversely, men with higher 1,25(OH)₂D had lower baseline BMD. 1,25(OH)₂D was not associated with BMD loss or nonvertebral fracture. Compared with higher levels of calcitriol, the risk of hip fracture was higher in men with the lowest 1,25(OH)₂D levels (8.70 to 51.60 pg/mL) after adjustment for baseline hip BMD (hazard ratio [HR] = 1.99, 95% confidence interval [CI] 1.19–3.33). Adjustment of 1,25(OH)₂D data for 25OHD (and vice versa) had little effect on the associations observed but did attenuate the hip fracture association of both vitamin D metabolites. In older men, higher 1,25(OH)₂D was associated with lower baseline BMD but was not related to the rate of bone loss or nonvertebral fracture risk. However, with BMD adjustment, a protective association for hip fracture was found with higher 1,25(OH)₂D. The associations of 25OHD with skeletal outcomes were generally stronger than those for 1,25(OH)₂D. These results do not support the hypothesis that measures of 1,25(OH)₂D improve the ability to predict adverse skeletal outcomes when 25OHD measures are available. © 2015 American Society for Bone and Mineral Research.     

Low Vitamin D Status Is Associated With Impaired Bone Quality and Increased Risk of Fracture-Related Hospitalization in Older Australian Women

The vitamin D debate relates in part to ideal public health population levels of circulating 25-hydroxyvitamin D (25OHD) to maintain bone structure and reduce fracture. In a secondary analysis of 1348 women aged 70 to 85 years at baseline (1998) from the Perth Longitudinal Study of Aging in Women (a 5-year calcium supplementation trial followed by two 5-year extensions), we examined the dose-response relations of baseline plasma 25OHD with hip DXA BMD at year 1, lumbar spine BMD, and trabecular bone score (TBS) at year 5, and fracture-related hospitalizations over 14.5 years obtained by health record linkage. Mean baseline plasma 25OHD was 66.9 ± 28.2 nmol/L and 28.5%, 36.4%, and 35.1% of women had levels <50, 50 to 74.9, and ≥75 nmol/L, respectively. Generalized additive models showed that total hip and femoral neck BMD and TBS, but not spine BMD, were higher with increasing plasma 25OHD up to 100 nmol/L. Compared with those with 25OHD <50 nmol/L, women with 25OHD ≥75 nmol/L had significantly higher total hip and femoral neck BMD at year 1 (3.3% to 3.9%) and TBS at year 5 (2.0%), all P < 0.05. During the follow-up, 27.6% of women experienced any fracture-related hospitalization and 10.6% hip fracture-related hospitalization. Penalized spline regression models showed a decrease in risk with increased 25OHD levels up to 65 nmol/L and 75 nmol/L for hip fracture and any fracture-related hospitalization, respectively. Cox regression grouped analyses showed that compared with women with 25OHD <50 nmol/L, those with 25OHD levels 50 to 74.9 and ≥75 nmol/L had significantly lower risk for hip fracture [HR 0.60 (95% CI, 0.40 to 0.91) and 0.61 (95% CI, 0.40 to 0.92), respectively], and any fracture-related hospitalization [HR 0.77 (95% CI, 0.59 to 0.99) and 0.70 (95% CI, 0.54 to 0.91), respectively]. In older white women, 25OHD levels >50 nmol/L are a minimum public health target and 25OHD levels beyond 75 nmol/L may not have additional benefit to reduce fracture risk. © 2019 American Society for Bone and Mineral Research.     

Leptin,Body Composition and Bone Mineral Density in Premenopausal Women

Body weight is known to be associated with bone mass, however, it is unclear whether body composition, as reflected by the percent of total weight that is fat tissue (%fat), is associated with bone mass independently of weight. Fat tissue is metabolically active, and hormonal factors may mediate an association of %fat with bone mass. Leptin, a hormone produced in fat tissue, has recently been shown to be inversely related to bone mass in mice, but whether it is related to human bone mass is uncertain. We sought to investigate the associations of %fat and of serum leptin concentration with bone mineral density (BMD) in a cohort of 153 premenopausal women. BMD measurements of the total hip, lumbar spine and total body as well as body composition were measured by dual energy X-ray absorptiometry (DXA). Serum leptin levels were established using a commercial competitive binding assay. Individually, body weight, %fat and leptin were each positively associated with BMD at all three sites. However, when we examined BMD either as a function of both body weight and %fat together, or as a function of both body weight and leptin together, we found that for a given body weight, BMD appeared to be inversely associated with %fat and similarly appeared to be inversely associated with leptin. When BMD was examined as a function of %fat and leptin together, we found that for a given %fat, leptin appeared to be inversely associated with BMD. In summary, the results of this study suggest that for a given body weight, a higher proportion of fat and a higher serum leptin concentration have negative associations with bone mass in premenopausal women. This material is based on work supported by the U.S. Department of Agriculture, under agreement No. 58-1950-9-001. Any questions, findings, conclusions, or recommendations expressed in this publication are those of the authors, and do not necessarily reflect the view of the U.S. Department of Agriculture. This work was presented in part as an abstract at the ASBMR meeting in October 2001.     

Age-Related Changes in Bone Density,Microarchitecture, and Strength in Postmenopausal Black and White Women: The SWAN Longitudinal HR-pQCT Study

Higher fracture risk in White versus Black women is partly explained by lower BMD and worse bone microarchitecture in White women. However, whether rates of decline in bone density, microarchitecture and strength differ between postmenopausal Black and White women is unknown. Further, factors that influence rates of age-related bone microarchitecture deterioration remain ill-defined. Thus, over 6.7 years, longitudinal changes were measured in peripheral volumetric bone mineral density (vBMD), microarchitecture, and strength at the distal radius and tibia using HR-pQCT in postmenopausal Black (n = 80) and White (n = 137) women participating in the Study of Women's Health Across the Nation. It was assessed whether age-related changes in vBMD and microarchitecture were influenced by body weight, body composition, and/or weight change. It was found that at the radius, where White women appeared to have slightly greater rates of loss in total vBMD, cortical bone volume, and porosity than Black women, those differences were attenuated after adjusting for clinical covariates. At the tibia, Black and White women had similar rates of bone loss. Independent of race and other clinical covariates, women with the lowest baseline body weight experienced the greatest decline in total and trabecular vBMD at the radius. Furthermore, women who lost weight over the follow-up period had higher rates of bone loss, particularly at the tibia, compared with those who maintained or gained weight. Higher baseline total body fat mass was also protective of bone loss at both the radius and tibia. In conclusion, these findings indicate that lower fracture risk among postmenopausal Black women is not caused by slower rates of bone deterioration, and highlight the importance for postmenopausal women to avoid lower body weight and excessive weight loss to avert rapid bone loss and subsequent fractures. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Association Between Abdominal Aortic Calcification,Bone Mineral Density,and Fracture in Older Women

Although a relationship between vascular disease and osteoporosis has been recognized, its clinical importance for fracture risk evaluation remains uncertain. Abdominal aortic calcification (AAC), a recognized measure of vascular disease detected on single-energy images performed for vertebral fracture assessment, may also identify increased osteoporosis risk. In a prospective 10-year study of 1024 older predominantly white women (mean age 75.0 ± 2.6 years) from the Perth Longitudinal Study of Aging cohort, we evaluated the association between AAC, skeletal structure, and fractures. AAC and spine fracture were assessed at the time of hip densitometry and heel quantitative ultrasound. AAC was scored 0 to 24 (AAC24) and categorized into low AAC (score 0 and 1, n = 459), moderate AAC (score 2 to 5, n = 373), and severe AAC (score > 6, n = 192). Prevalent vertebral fractures were calculated using the Genant semiquantitative method. AAC24 scores were inversely related to hip BMD ( r _s = –0.077, p = 0.013), heel broadband ultrasound attenuation ( r _s = –0.074, p = 0.020), and the Stiffness Index ( r _s = –0.073, p = 0.022). In cross-sectional analyses, women with moderate to severe AAC were more likely to have prevalent fracture and lumbar spine imaging-detected lumbar spine fractures, but not thoracic spine fractures (Mantel-Haenszel test of trend p < 0.05). For 10-year incident clinical fractures and fracture-related hospitalizations, women with moderate to severe AAC (AAC24 score >1) had increased fracture risk (HR 1.48; 95% CI, 1.15 to 1.91; p = 0.002; HR 1.46; 95% CI, 1.07 to 1.99; p = 0.019, respectively) compared with women with low AAC. This relationship remained significant after adjusting for age and hip BMD for clinical fractures (HR 1.40; 95% CI, 1.08 to 1.81; p = 0.010), but was attenuated for fracture-related hospitalizations (HR 1.33; 95% CI, 0.98 to 1.83; p = 0.073). In conclusion, older women with more marked AAC are at higher risk of fracture, not completely captured by bone structural predictors. These findings further support the concept that vascular calcification and bone pathology may share similar mechanisms of causation that remain to be fully elucidated © 2019 American Society for Bone and Mineral Research     

Vitamin D and Bone Mineral Density in Ambulatory Women Living in Buenos Aires, Argentina

The aim of this study was to determine possible associations between bone mineral density (BMD), 25-hydroxyvitamin D (25(OH)D) and intact parathyroid hormone (PTH). In a retrospective study we examined the case notes of free-living postmenopausal women living in our city (34° S). We also report a low prevalence of vitamin D deficiency (25(OH)D <25 nmol/l, 5.6%) and of secondary hyperparathyroidism (intact PTH >65 pg/ml, 7.5%). Age was correlated with BMD at the lumbar spine (r=−0.25, p = 0.00038) and femoral neck (r=−0.252, p = 0.0003). Body mass index (BMI) was correlated with BMD at the femoral neck (r= 0.177, p = 0.021) but not at the lumbar spine. 25(OH)D was positively correlated with BMD at the femoral neck (r = 0.149, p=0.036) but not at the lumbar spine. PTH was positively correlated with age (r= 0.279, p = 0.012) and negatively correlated with 25(OH)D (r=−0.322, p = 0.0036). PTH was also negatively correlated with BMD at the lumbar spine (r=−0.258, p=0.02) and the femoral neck (r=−0.282, p = 0.011). Forward stepwise multiple regression showed that BMI, age and 25(OH)D made significant contributions to BMD at the femoral neck. PTH also showed a significant contribution to BMD at both sites. In conclusion, weak correlations found between PTH and 25(OH)D and BMD suggest these biochemical variables, among other factors, contribute to lumbar spine and femoral neck BMD. Received: 19 February 2000 / Accepted: 20 June 2000     

The Vitamin D Metabolite Ratio Is Associated With Changes in Bone Density and Fracture Risk in Older Adults

Recent studies have suggested that 25-hydroxyvitamin D (25(OH)D) may be a poor biomarker of bone health, in part because measured levels incorporate both protein-bound and free vitamin D. The ratio of its catabolic product (24,25-dihydroxyvitamin D [24,25(OH)₂D]) to 25(OH)D (the vitamin D metabolite ratio [VMR]) may provide more information on sufficient vitamin D stores and is not influenced by vitamin D–binding protein concentrations. We evaluated whether the VMR or 25(OH)D are more strongly associated with bone loss and fracture risk in older adults. We performed a retrospective cohort study of 786 community-dwelling adults aged 70 to 79 years who participated in the Health Aging and Body Composition study. Our primary outcomes were annual changes in bone density and incident fracture. The mean age of these participants was 75 ± 3 years, 49% were female, 42% were Black, and 23% had an estimated glomerular filtration rate (eGFR) <60 mL/mL/1.73m². In fully adjusted models, a 50% lower VMR was associated with 0.3% (0.2%, 0.6%) more rapid decline in total hip bone mineral density (BMD). We found similar relationships with thoracic and lumbar spine BMD. In contrast, 25(OH)D₃ concentrations were not associated with longitudinal change in BMD. There were 178 fractures during a mean follow-up of 10 years. Each 50% lower VMR was associated with a 49% (95% confidence interval [CI] 1.06, 2.08) greater fracture risk, whereas lower 25(OH)D₃ concentrations were not significantly associated with fracture risk (hazard ratio [HR] per 50% lower 1.07 [0.80, 1.43]). In conclusion, among a diverse cohort of community-dwelling older adults, a lower VMR was more strongly associated with both loss of BMD and fracture risk compared with 25(OH)D₃. Trials are needed to evaluate the VMR as a therapeutic target in persons at risk for worsening BMD and fracture. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Vitamin D and Estrogen Receptor Polymorphisms and Bone Mineral Changes in Postpartum Women

BsmI restriction fragment length polymorphism (RFLP) of the vitamin D receptor (VDR) gene and PvuII RFLPs of the estrogen receptor (ER) gene and their relation to changes in areal bone mineral density (BMD) were examined in 43 healthy postpartum Finnish women aged 31.3 (SD 4.7) years. BMD was measured by dual energy X-ray absorptiometry at lumbar spine, right femoral neck, and dominant distal radius immediately after delivery, 1 month after resumption of menses, and 1 year thereafter. The RFLPs were represented as Bb (BsmI) and Pp (PvuII), the capital letters denoting the absence of and the small letters the presence of the restriction sites. The frequency of VDR alleles was as follows: bb (20.9%), Bb (60.5%), and BB (18.6%), and that of ER alleles was pp (39.5%), Pp (51.2%), and PP (9.3%). Altogether, BMD decreased significantly during postpartum amenorrhea at all sites [the mean bone loss ranging from −1.2 (SD 3.6)% at the distal radius to −3.7 (2.9)% at the femoral neck], and increased after resumption of menses [the 1-year follow-up BMD values ranging from −1.0 (2.4)% at the femoral neck to +3.3 (4.0)% at the lumbar spine as compared with baseline]. No obvious genotype-related differences were found between these changes. These results suggest that the BsmI and PvuII polymorphisms may not have substantial influence on BMD changes postpartum. Received: 20 November 1998 / Accepted: 30 September 1999     

Effects of 24 Months of Treatment With Romosozumab Followed by 12 Months of Denosumab or Placebo in Postmenopausal Women With Low Bone Mineral Density: A Randomized,Double‐Blind,Phase 2, Parallel Group Study

Over 12 months, romosozumab increased bone formation and decreased bone resorption, resulting in increased bone mineral density (BMD) in postmenopausal women with low BMD (NCT00896532). Herein, we report the study extension evaluating 24 months of treatment with romosozumab, discontinuation of romosozumab, alendronate followed by romosozumab, and romosozumab followed by denosumab. Postmenopausal women aged 55 to 85 years with a lumbar spine (LS), total hip (TH), or femoral neck T‐score ≤–2.0 and ≥–3.5 were enrolled and randomly assigned to placebo, one of five romosozumab regimens (70 mg, 140 mg, 210 mg monthly [QM]; 140 mg Q3M; 210 mg Q3M) for 24 months, or open‐label alendronate for 12 months followed by romosozumab 140 mg QM for 12 months. Eligible participants were then rerandomized 1:1 within original treatment groups to placebo or denosumab 60 mg Q6M for an additional 12 months. Percentage change from baseline in BMD and bone turnover markers (BTMs) at months 24 and 36 and safety were evaluated. Of 364 participants initially randomized to romosozumab, placebo, or alendronate, 315 completed 24 months of treatment and 248 completed the extension. Romosozumab markedly increased LS and TH BMD through month 24, with largest gains observed with romosozumab 210 mg QM (LS = 15.1%; TH = 5.4%). Women receiving romosozumab who transitioned to denosumab continued to accrue BMD, whereas BMD returned toward pretreatment levels with placebo. With romosozumab 210 mg QM, bone formation marker P1NP initially increased after treatment initiation and gradually decreased to below baseline by month 12, remaining below baseline through month 24; bone resorption marker β‐CTX rapidly decreased after treatment, remaining below baseline through month 24. Transition to denosumab further decreased both BTMs, whereas after transition to placebo, P1NP returned to baseline and β‐CTX increased above baseline. Adverse events were balanced between treatment groups through month 36. These data suggest that treatment effects of romosozumab are reversible upon discontinuation and further augmented by denosumab. © 2018 The Authors Journal of Bone and Mineral Research published by Wiley Periodicals, Inc.     

Relationships Among Bone Mineral Density,Body Composition,and Isokinetic Strength in Young Women

The purpose of this study was to examine the relationships among bone mineral density (BMD), body composition, and isokinetic strength in young women. Subjects were 76 women (age: 20 ± 2 yr, height: 164 ± 6 cm, weight: 57 ± 6 kg, body fat: 27 ± 4%) with a normal body mass index (18–25 kg/m²). Total body, nondominant proximal femur, and nondominant distal forearm BMD were measured with dual-energy x-ray absorptiometry. Isokinetic concentric (CON) and eccentric (ECC) strength of the nondominant thigh and upper arm were measured at 60 deg/sec. Fat-free mass (FFM) correlated (P < 0.001) with BMD of the total body (r = 0.56) and femoral neck (r = 0.52), whereas fat mass (FM) did not relate to BMD at any site. Leg FFM, but not FM, correlated with BMD in all regions of interest at the proximal femur. Weak associations were observed between arm FFM and forearm BMD. Isokinetic strength did not relate to BMD at any site after correcting for regional FFM. In conclusion, strong, independent associations exist between BMD and FFM, but not FM or isokinetic strength, in young women.     

The Association between Parathyroid Hormone, Vitamin D and Bone Mineral Density in 70-Year-Old Icelandic Women

Parathyroid hormone (PTH) may be an important determinant of cortical bone remodeling in the elderly. Vitamin D status is one of the determining factors in this relationship. The aim of this study was to quantify the relationship between serum PTH, vitamin D and bone mineral density (BMD) in elderly women in Reykjavik (64° N), where daily intake of cod liver oil is common and mean calcium intake is high. ln PTH correlated inversely with 25(OH)D (r=−0.26, p<0.01). In multivariate analysis PTH correlated inversely with whole body BMD (mostly cortical bone) (R ²= 2.2%, p = 0.04) but not with the lumbar spine BMD, reflecting more cancellous bone. No association was found between 25(OH)D levels and BMD at any site in univariate or multivariate analysis. Osteocalcin, a measure of bone turnover, was negatively associated with BMD and this association remained significant when corrected for PTH levels. In summary, in this fairly vitamin D replete population with high calcium intake, PTH was negatively associated with total body BMD. We infer that suppression of PTH may reduce cortical bone loss, but other factors are likely to contribute to age-related bone remodeling and osteoporosis. Received: 3 January 2000 / Accepted: 10 April 2000     

Effect of Two‐Year Caloric Restriction on Bone Metabolism and Bone Mineral Density in Non‐Obese Younger Adults: A Randomized Clinical Trial

Although caloric restriction (CR) could delay biologic aging in humans, it is unclear if this would occur at the cost of significant bone loss. We evaluated the effect of prolonged CR on bone metabolism and bone mineral density (BMD) in healthy younger adults. Two‐hundred eighteen non‐obese (body mass index [BMI] 25.1 ± 1.7 kg/m²), younger (age 37.9 ± 7.2 years) adults were randomly assigned to 25% CR (CR group, n = 143) or ad libitum (AL group, n = 75) for 2 years. Main outcomes were BMD and markers of bone turnover. Other outcomes included body composition, bone‐active hormones, nutrient intake, and physical activity. Body weight (–7.5 ± 0.4 versus 0.1 ± 0.5 kg), fat mass (–5.3 ± 0.3 versus 0.4 ± 0.4 kg), and fat‐free mass (–2.2 ± 0.2 versus –0.2 ± 0.2 kg) decreased in the CR group compared with AL (all between group p < 0.001). Compared with AL, the CR group had greater changes in BMD at 24 months: lumbar spine (–0.013 ± 0.003 versus 0.007 ± 0.004 g/cm²; p < 0.001), total hip (–0.017 ± 0.002 versus 0.001 ± 0.003 g/cm²; p < 0.001), and femoral neck (–0.015 ± 0.003 versus –0.005 ± 0.004 g/cm²; p = 0.03). Changes in bone markers were greater at 12 months for C‐telopeptide (0.098 ± 0.012 versus 0.025 ± 0.015 μg/L; p < 0.001), tartrate‐resistant acid phosphatase (0.4 ± 0.1 versus 0.2 ± 0.1 U/L; p = 0.004), and bone‐specific alkaline phosphatase (BSAP) (–1.4 ± 0.4 versus –0.3 ± 0.5 U/L; p = 0.047) but not procollagen type 1 N‐propeptide; at 24 months, only BSAP differed between groups (–1.5 ± 0.4 versus 0.9 ± 0.6 U/L; p = 0.001). The CR group had larger increases in 25‐hydroxyvitamin D, cortisol, and adiponectin and decreases in leptin and insulin compared with AL. However, parathyroid hormone and IGF‐1 levels did not differ between groups. The CR group also had lower levels of physical activity. Multiple regression analyses revealed that body composition, hormones, nutrients, and physical activity changes explained ～31% of the variance in BMD and bone marker changes in the CR group. Therefore, bone loss at clinically important sites of osteoporotic fractures represents a potential limitation of prolonged CR for extending life span. Further long‐term studies are needed to determine if CR‐induced bone loss in healthy adults contributes to fracture risk and if bone loss can be prevented with exercise. © 2015 American Society for Bone and Mineral Research.     

Relationships Between Body Composition, Muscular Strength, and Bone Mineral Density in Estrogen-Deficient Postmenopausal Women

The purpose of this study was to examine relationships between muscular strength, body composition, and bone mineral density (BMD) in untrained postmenopausal women who are not on hormone replacement therapy (HRT). Fifty-five women (age: 63.3 ± 0.6 yr) completed menstrual history, physical activity, and calcium intake questionnaires. Total and regional body composition and total body, anteroposterior lumbar spine, nondominant forearm, and right proximal femur BMD were measured using dual-energy X-ray absorptiometry (DXA) (GE Lunar Prodigy, Prodigy enCORE software version 10.50.086, Madison, WI). Participants performed strength tests for 3 upper body and 5 lower body resistance exercises. Women with a relative skeletal muscle mass index (RSMI) value less than 5.45 kg/m² were defined as a sarcopenia group (SAR). SAR had significantly (p < 0.05) lower total body and forearm BMD compared with those who were not sarcopenic. BMD sites were significantly correlated with upper body strength (UBS) and lower body strength (LBS) (r = 0.28–0.50, p < 0.01), with the strength of relationship being site specific. Strength and fat mass (FM) significantly predicted total body BMD (R² = 0.232–0.241, p < 0.05), FM variables predicted spine BMD (R² = 0.109–0.140, p < 0.05), and LBS and RSMI predicted hip BMD sites (R² = 0.073–0.237, p < 0.05). Body composition variables failed to significantly predict LBS. In conclusion, the contribution of body composition and strength variables to BMD varied by site as FM was more important for total body, forearm and spine BMD, and LBS exerted greater influence on the hip sites.     

Vitamin D Receptor Gene Polymorphisms and Bone Mineral Density in Elderly Chinese Men and Women in Hong Kong

Although genetic factors have been strongly implicated in determining bone mineral density (BMD), the role of the vitamin D receptor (VDR) polymorphism remains controversial. An overall consensus is difficult, as the populations studied have been heterogeneous with respect to menopausal status and ethnicity. Moreover, some studies have examined only small populations, and relatively few studies have been conducted in Asian populations. There is mounting evidence that calcium homeostasis in Asian populations differs from that in Caucasians. This difference may be mediated, in part, through VDR effects. In a cross-sectional study we have examined the relationship between the VDR polymorphism and BMD in 272 women (mean age 75 years) and 237 men (mean age 73 years) of Chinese origin from Hong Kong. Consistent with other studies in Asian populations we found higher frequencies of the T, b and a alleles compared with those reported in Caucasian populations. Moreover, no significant difference in BMD was observed when subjects were grouped by a combination of the genotypes (bbAATT, bbAaTT, bbaaTT, BbAaTt, BbAATt). These results suggest that VDR polymorphism is not associated with BMD in elderly Hong Kong Chinese men and women. Received: 16 July 1998 / Accepted: 15 February 1999