Hip Bone Mineral Density Loss Research Articles

High-dose vitamin D to attenuate bone loss in patients with prostate cancer on androgen deprivation therapy: A phase 2 RCT.

Androgen deprivation therapy (ADT) inhibits prostate cancer growth. However, ADT causes loss of bone mineral density (BMD) and an increase in fracture risk; effective interventions for ADT-induced bone loss are limited. A phase 2 randomized controlled trial investigated the feasibility, safety, and preliminary efficacy of high-dose weekly vitamin D (HDVD, 50,000 IU/week) versus placebo for 24 weeks in patients with prostate cancer receiving ADT, with all subjects receiving 600 IU/day vitamin D and 1000 mg/day calcium. Participants were ≥60 years (mean years, 67.7), had a serum 25-hydroxyvitamin D level <32 ng/mL, and initiated ADT within the previous 6 months. At baseline and after intervention, dual-energy x-ray absorptiometry was used to assess BMD, and levels of bone cell, bone formation, and resorption were measured. The HDVD group (N=29) lost 1.5% BMD at the total hip vs. 4.1% for the low-dose group (N=30; p=.03) and 1.7% BMD at the femoral neck vs. 4.4% in the low-dose group (p=.06). Stratified analyses showed that, for those with baseline 25-hydroxyvitamin D level <27 ng/mL, the HDVD group lost 2.3% BMD at the total hip vs 7.1% for the low-dose group (p<.01). Those in the HDVD arm showed significant changes in parathyroid hormone (p<.01), osteoprotegerin (p<0.01), N-terminal telopeptide of type 1 collagen (p<0.01) and C-terminal telopeptide of type 1 collagen (p<0.01). No difference in adverse events or toxicity was noted between the groups. HDVD supplementation significantly reduced hip and femoral neck BMD loss, especially for patients with low baseline serum 25-hydroxyvitamin D levels, although demonstrating safety and feasibility in prostate cancer patients on ADT.

More rapid bone mineral density loss in older men with diabetes: The Osteoporotic Fractures in Men (MrOS) Study.

Type 2 diabetes mellitus (T2D) is associated with more rapid bone loss in women, but less evidence is available for men or those with prediabetes. To determine whether bone loss rate is affected by diabetes status in older men, we analyzed data from the Osteoporotic Fractures in Men (MrOS) study. The multisite MrOS study enrolled 5,994 men aged ≥65 years. Diabetes status was defined by self-report, diabetes medication use, or elevated fasting serum glucose at baseline. Hip bone mineral density (BMD) was measured by dual energy x-ray absorptiometry (DXA) at baseline and a follow-up visit after 4.6 ± 0.4 years. This analysis included 4095 men, excluding those without a follow-up DXA or with unknown diabetes status. Changes in hip BMD in participants with normoglycemia (NG), prediabetes, or T2D, excluding thiazolidinedione (TZD) users, were evaluated using generalized linear models (GLM). Diabetes medication use and BMD loss among those with T2D were also evaluated with GLM. In adjusted models, loss in hip BMD was greater in men with T2D (- 2.23%: 95% CI: -2.54 to -1.91; p<0.001) but not in men with prediabetes (-1.45%; 95% CI -1.63 to -1.26; p=0.33) compared to NG (-1.57%: 95% CI -1.73 to -1.41). Among men with T2D, TZD, insulin and sulfonylurea use were associated with greater hip BMD loss. Men with T2D, but not prediabetes, experienced an accelerated bone loss compared to participants with normoglycemia. More rapid bone loss predicts increased risk of fractures and mortality in broader populations.

Longitudinal Assessment of Bone Mineral Density in Women Living With and Without HIV Across Reproductive Phases.

Women living with HIV commonly experience low areal bone mineral density (BMD), but whether this is affected by low ovarian hormonal states (prolonged amenorrhea or menopause) is unknown. We compared rates of BMD loss between women living with HIV and HIV-negative control women and investigated its association with low ovarian hormonal states. Women living with HIV were enrolled from Vancouver Canada and controls from 9 Canadian sites. This longitudinal analysis included age-matched women living with HIV in the Children and Women: AntiRetrovirals and Markers of Aging cohort and controls in the population-based Canadian Multicentre Osteoporosis Study. Rate of change/year in BMD at the total hip and lumbar spine (L1-L4) between 3 and 5 years was compared between groups, adjusting for sociodemographic and clinical variables. Ninety-two women living with HIV (median [interquartile range] age: 49.5 [41.6-54.1] years and body mass index: 24.1 [20.7-30.8] kg/m 2 ) and 278 controls (age: 49.0 [43.0-55.0] years and body mass index: 25.8 [22.9-30.6] kg/m 2 ) were included. Total hip BMD loss was associated with HIV (β: -0.003 [95% CI: -0.006 to -0.0001] g/cm 2 /yr), menopause (β: -0.007 [-0.01 to -0.005] g/cm 2 /yr), and smoking (β: -0.003 [-0.006 to -0.0002] g/cm 2 /yr); BMD gain was linked with higher body mass index (β: 0.0002 [0.0007-0.0004] g/cm 2 /yr). Menopause was associated with losing L1-L4 BMD (β: -0.01 [-0.01 to -0.006] g/cm 2 /yr). Amenorrhea was not associated with BMD loss. HIV and menopause negatively influenced total hip BMD. These data suggest women living with HIV require hip BMD monitoring as they age.

Increased Imminent Fracture Risk in Liver Transplant Recipients Despite Bisphosphonate Therapy

Bone loss is significant after orthotopic liver transplant (OLT) and is associated with increased fracture risk and decreased quality of life. In post-transplant fracture prevention, the cornerstone of therapeutic management is bisphosphonates. We conducted a retrospective study in a cohort of 155 OLT recipients who received a bisphosphonate prescription at hospital discharge between 2012 and 2016 to investigate post-OLT fragility fracture incidence and predictive risk factors. Before OLT, 14 patients presented a T score < -2.5 SD, and 23 patients (14.8%) had a history of fracture. During follow-up, the cumulative incidence of fractures on bisphosphonates (99.4% risedronate/alendronate) was 9.7% at 12 months and 13.1% at 24 months. The median time to first fragility fracture was 10 months (IQR, 3-22 months) and thus within the first 2 years of follow-up. Predictive factors of fragility fractures in multivariate Cox regression analyses included age 60 years or older (hazard ratio [HR], 2.61; 95% CI, 1.14-6.01; P=.02), post-transplant diabetes mellitus (HR, 3.82; 95% CI, 1.55-9.44; P=.004), and cholestatic disease (HR, 5.93; 95% CI, 2.30-15.26; P=.0002). Additionally, the female sex was associated with a strong trend toward increased fracture risk in univariate analysis (HR, 2.27; 95% CI, 1.00-5.15; P=.05), as well as a post-transplant absolute decrease in bone mineral density at the femoral neck and total hip (P=.08). This real-world study reports a high incidence of fractures post-OLT despite bisphosphonate therapy. Age 60 years or older, post-transplant diabetes mellitus, cholestatic disease, female sex, and femoral neck and/or total hip bone mineral density loss contribute to increased imminent fracture risk in liver transplant recipients.

Sex-specific differences in bone mineral density loss after sleeve gastrectomy

Sleeve gastrectomy is an effective bariatric procedure; however, sleeve gastrectomy-related adverse skeletal outcomes have been increasingly reported. High levels of sex hormone-binding globulin (SHBG) have been documented to be a risk factor of bone mineral density (BMD) loss with different effects observed between sexes. The aim of this study was to identify sex-specific changes in BMD following sleeve gastrectomy and to evaluate the role of SHBG in this process. This retrospective study included 19 middle-aged men and 30 non-menopausal women with obesity who underwent sleeve gastrectomy in China. Anthropometrics, bone turnover markers, calciotropic hormones, BMD, SHBG, and gonadal steroids were measured preoperatively and at 6 and 12 months postoperatively. Longitudinal changes in BMD, bone turnover markers and SHBG were compared between sexes by linear mixed models. Multiple stepwise regression analysis was used to identify the predictors of BMD loss at the investigated bone sites. Over the 12-month study period, total hip and femoral neck BMD decreased, while lumbar spine BMD remained largely unchanged in both sexes. Linear mixed models revealed significant sex × time interaction effects in total hip BMD and SHBG, showing that men had a significantly greater reduction in total hip BMD and less increase in SHBG after sleeve gastrectomy than women. In the multivariate model, SHBG was significantly associated with total hip BMD loss in men (adjusted β = -0.533, P = 0.019) but not women while total estrogen was significantly associated with total hip BMD loss in women (adjusted β = 0.508, P = 0.01) but not men. Significant sex-specific BMD changes were observed after sleeve gastrectomy in the current study. Sleeve gastrectomy-related increase in SHBG may be a specific risk factor for total hip BMD loss in men. Our results indicate that sex-specific screening may be warranted to facilitate personalized postoperative bone care in this population.

Prunes preserve hip bone mineral density in a 12-month randomized controlled trial in postmenopausal women: the Prune Study

Dietary consumption of prunes has favorable impacts on bone health, but more research is necessary to improve upon study designs and refine our understandings. We evaluated the effects of prunes (50g or 100g/d) on bone mineral density (BMD) in postmenopausal women during a 12-mo dietary intervention. Secondary outcomes include effects on bone biomarkers. The single-center, parallel-arm 12-mo randomized controlled trial tested the effects of 50 g and 100 g prunes compared with a control group on BMD (every 6 mo) and bone biomarkers in postmenopausal women. In total, 235 women (age 62.1± 5.0y) were randomly allocated into control (n=78), 50-g prune (n=79), or 100-g prune (n=78) groups. Compliance was 90.2±1.8% and 87.1±2.1% in the 50-g and 100-g prune groups. Dropout was 22%; however, the dropout rate was 41% for the 100-g prune group (compared with other groups: 10%, control; 15%, 50g prune; P<0.001). A group×time interaction for total hip BMD was observed in control compared with 50-g prune groups (P<0.05) but not in control compared with 100-g prune groups (P>0.05). Total hip BMD decreased -1.1±0.2% in the control group at 12 mo, whereas the 50-g prune group preserved BMD (-0.3±0.2%) at 12 mo (P<0.05). Although hip fracture risk (FRAX) worsened in the control group at 6 mo compared with baseline (10.3±0.5% compared with 9.8±0.5%, P<0.05), FRAX score was maintained in the pooled (50 g+100g) prune groups. A 50-g daily dose of prunes can prevent loss of total hip BMD in postmenopausal women after 6 mo, which persisted for 12 mo. Given that there was high compliance and retention at the 50-g dosage over 12 mo, we propose that the 50-g dose represents a valuable nonpharmacologic treatment strategy that can be used to preserve hip BMD in postmenopausal women and possibly reduce hip fracture risk. This trial was registered at clinicaltrials.gov as NCT02822378.

Low Dose Daily Prunes Preserve Hip Bone Mineral Density With No Impact on Body Composition in a 12-Month Randomized Controlled Trial in Postmenopausal Women: The Prune Study

ObjectivesDietary consumption of prunes has favorable impacts on bone health, however, more research is necessary to improve upon study designs and refine our understandings and determine whether unfavorable fat gain occurs with long-term treatment. Objectives: Evaluate the effects of prunes (50g and 100g/day) on bone mineral density (BMD) in postmenopausal women during a 12-month dietary intervention. Secondary outcomes include effects on body composition. MethodsSingle center, parallel arm 12-month randomized controlled trial (RCT; NCT02822378) to test effects of 50g and 100g/day prunes vs. a Control group on BMD (dual-energy X-ray absorptiometry) (every 6 months) and body composition in postmenopausal women with a BMD T-score of < 0.0 and >–3.0 at any site. Results235 women (age 62.1 ± 5.0 yr) were randomized into Control (n = 78), 50 g Prune (n = 79), or 100 g Prune (n = 78) groups. Compliance was 90.2 ± 1.8% and 87.1 ± 2.1% in the 50 g and 100 g Prune groups. Dropout was 22%; however, the dropout rate was 41% for the 100 g Prune group compared to other groups (10% Control; 15% 50 g Prune; (p < 0.001)). A group × time interaction for total hip BMD was observed in Control vs 50 g Prune groups (p = 0.030), but not in Control vs 100 g Prune groups (p = 0.194). Prune consumption did not affect body mass in 50 g prune (p = 0.837) or 100 g prune (p = 0.121) groups compared to Control. A group × time interaction for fat mass was observed in Control vs 100 g Prune groups (p = 0.031), but not in Control vs 50 g Prune groups (p = 0.792). ConclusionsA 50 g dose of daily dose of prunes can prevent loss of total hip BMD in postmenopausal women, without increased fat mass seen with the larger dose. Given that there was high compliance and retention at the 50 g dosage over 12 months, we propose that the 50 g dose represents a valuable non-pharmacological treatment strategy that can be used to preserve hip BMD in postmenopausal women, without increasing body or fat mass. Funding SourcesCalifornia Prune Board

Examining zoledronic acid for the prevention of bone loss in patients receiving bariatric surgery

PurposeBariatric surgery is an effective treatment for severe obesity but causes substantial bone loss and increased risk of fractures. To date, there have been no studies examining whether pharmacologic treatments can prevent bone loss after bariatric surgery. We performed an exploratory study to examine the preliminary safety and efficacy of zoledronic acid (ZOL), a potent anti-resorptive bisphosphonate, to suppress bone turnover markers (BTM) and prevent declines in bone mineral density (BMD) after Roux-en-Y gastric bypass (RYGB) surgery. MethodsWe performed an open-label pilot study of pre-operative ZOL in postmenopausal women with obesity who were planning RYGB (n = 4). A single dose of zoledronic acid 5 mg was given intravenously prior to RYGB. Serum bone biochemistries including C-telopeptide (CTX) and procollagen type 1 N-terminal propeptide (P1NP) were measured at multiple timepoints throughout the 24-week study. BMD was also obtained at the spine and hip by dual-energy x-ray absorptiometry (DXA) and at the trabecular spine by quantitative computed tomography (QCT) at pre-operative baseline and 24 weeks. Results were compared against pre-operative baseline and against changes among RYGB historical controls (n = 10). ResultsAt 2 weeks after RYGB, there was a nonsignificant trend for CTX and P1NP levels to be lower than baseline levels in the ZOL group. By 24 weeks after RYGB, however, participants who received ZOL had a significant increase in CTX above pre-operative baseline (+0.228 ± 0.117 ng/dL, p = 0.030) but this CTX rise was less than that observed in the controls (+0.601 ± 0.307 ng/dL, p = 0.042 between groups). Despite ZOL use, participants had significant areal BMD loss at the total hip as compared to pre-operative baseline (−4.2 ± 1.5%, p = 0.012) that was similar in magnitude to total hip BMD loss in the controls (−5.5 ± 3.9%, p = 0.005). There was a suggestion that the ZOL group might be protected against trabecular spine volumetric bone loss as compared to the control group (+4.8 ± 8.0% vs. -5.9 ± 7.0%, p = 0.075 between groups). Serum calcium, 25-hydroxyvitamin D, and parathyroid hormone did not change in either group. No hypocalcemia or serious adverse events were reported after ZOL. ConclusionIn this proof of concept study, a single dose of ZOL prior to RYGB appeared to transiently mitigate but not fully prevent high bone turnover in the acute postoperative period. At 24 weeks after RYGB, our preliminary data suggest that ZOL was not sufficient to prevent bone loss at the hip, although it may preserve bone density at the trabecular spine. Further prospective, controlled studies are needed to confirm our findings and to identify the best strategies for preventing bone loss in bariatric patients receiving RYGB.

Bone Mineral Density in Different Menopause Stages is Associated with Follicle Stimulating Hormone Levels in Healthy Women.

Although estradiol (E2) has been believed to be the most critical factor in the menopause-associated decrease in bone mineral density (BMD), the role of increasing follicle stimulating hormone (FSH) during menopause is relatively unclear. We determined the extent to which hip and lumbar spine BMD differ among the stages of menopause in healthy women, and whether BMD is associated with FSH and E2 levels. A cross-sectional study of 141 healthy women classified as premenopausal (Pre; 38 ± 6 yrs; mean ± SD, n = 30), early perimenopausal (EPeri; 50 ± 3yrs, n = 31), late perimenopausal (LPeri; 50 ± 4yrs, n = 30), early postmenopausal (EPost; 55 ± 3yrs, n = 24), or late postmenopausal (LPost; 62 ± 4 yrs, n = 26), was conducted. Spine/hip BMD and sex hormones were measured using dual-energy X-ray absorptiometry and enzymatic/colorimetric methods, respectively. Compared to EPeri, spine BMD was lower (p < 0.05) in LPeri, EPost, and LPost and hip BMD was lower (p < 0.05) in EPost and LPost. BMD was inversely associated with FSH (spine: r = −0.341; hip: r = −0.271, p < 0.05) and directly associated with E2 (spine: r = 0.274; hip: r = 0.256, p < 0.05). The menopause-related loss of spine and hip BMD is associated not only with low E2 but also higher FSH. Future studies are essential to delineating the mechanisms by which FSH regulates bone health in aging women.

Fractures After Denosumab Discontinuation: A Retrospective Study of 797 Cases.

ABSTRACTA rebound of osteoclast activity during the 2 years after a treatment or prevention of osteoporosis with denosumab (Dmab) leads to an increased risk of vertebral fractures (VFs). We attempted to identify the risk factors for these VF and to examine the protective role of bisphosphonates. For that, 22 specialists in Switzerland provided data of unselected patients, treated with denosumab for osteoporosis or breast cancer without metastases under aromatase inhibitors, who have received at least two injections of Dmab, with at least 1 year of follow‐up after discontinuation. The questionnaire covered separately the periods before, during, and after Dmab treatment, and registered clinical, radiological, and lab data. For the analysis of the risk factors, the main outcomes were the time to the first VF after the treatment, the presence of multiple VFs (MVFs), and the number of VFs. The incidence of VF was 16.4% before, 2.2% during, and 10.3% after the treatment with Dmab. The risk of VF after Dmab discontinuation was associated with an increased risk of non‐vertebral fractures. The pretreatment predictors of the post‐treatment fracture risk were a parental hip fracture and previous VFs. Further risk factors appeared later, such as low total hip bone mineral density (BMD) during and after denosumab, increased bone resorption markers, and the loss of total hip BMD after the denosumab. Treatment with bisphosphonates, especially after Dmab, had a protective effect. Bisphosphonates given before Dmab did not further decrease the risk of VF in cases who got bisphosphonates after Dmab. This study shows that the risk of VF is poorly predictable before the prescription of denosumab. But during and after the treatment, bone resorption markers and BMD have a significant predictive value. Bisphosphonates after the treatment with denosumab are protective against VFs. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Fracture risk and management of discontinuation of denosumab therapy: a systematic review and position statement by ECTS.

Denosumab discontinuation is characterized by an increase in bone turnover overriding pre-treatment status, a rapid bone loss in the majority and multiple vertebral fractures (VFx) in some patients. A working group of the European Calcified Tissue Society (ECTS) performed an updated systematic review of existing literature on changes of bone turnover, bone mineral density (BMD), and fracture risk after denosumab discontinuation and provided advice on management based on expert opinion. Important risk factors for multiple VFx following denosumab cessation are prevalent VFx, longer duration off therapy, greater gain in hip BMD during therapy, and greater loss of hip BMD after therapy according to a retrospective analysis of the FREEDOM Extension Study. Case series indicate that prior bisphosphonate therapy mitigates the biochemical rebound phenomenon after denosumab discontinuation, but it is uncertain whether this attenuation prevents BMD loss and fractures. Current evidence indicates partial efficacy of subsequent antiresorptive treatment with results seemingly dependent on duration of denosumab treatment. A careful assessment of indications to start denosumab treatment is advised, especially for younger patients. A case for long-term treatment with denosumab can be made for patients at high fracture risk already on denosumab treatment given the favorable efficacy and safety profile. In case of denosumab discontinuation, alternative antiresorptive treatment should be initiated 6 months after the final denosumab injection. Assessment of bone turnover markers may help define the optimal regimen, pending results of ongoing RCTs. Patients having sustained VFx should be offered prompt treatment to reduce high bone turnover.

High-dose vitamin D supplementation for cancer-treatment-induced bone loss in 164 breast and prostate cancer patients: A pooled analysis of two randomized controlled trials (RCTs).

12105 Background: Aromatase Inhibitor (AI) therapy and androgen deprivation therapy (ADT) significantly accelerate bone loss and increase fracture risk. Vitamin D (VITD) protects against bone loss, but it is unclear whether the recommended daily allowance (RDA; 600 IU/day for ages 51-70) of VITD is sufficient for cancer patients. Data from two RCTs were pooled to examine the safety and efficacy of high-dose VITD versus the RDA of VITD on bone mineral density (BMD). Methods: 164 breast and prostate cancer patients on AIs and ADT, respectively, with low VITD (&lt;32 ng/ml) were randomized to either high-dose VITD (50,000 IU/week; n=99) or placebo (n=65) for 24 weeks. All subjects received 600 IU/day of VITD. Of the 99 subjects assigned to high-dose VITD, 38 breast subjects also received the Exercise for Cancer Patients (EXCAP) program combining walking and resistance training. Serum VITD and calcium were assessed at weeks 0, 6, 12, 18, and 24. BMD was assessed at the hip and spine via DXA at weeks 0 and 24. The effect of high-dose VITD was tested via ANCOVA model adjusted for cancer type, baseline BMD and VITD. Results: High-dose VITD significantly reduced the amount of hip BMD loss versus the RDA of VITD (high-dose VITD: −0.8% vs placebo: −2.6%; p&lt;0.01) over 24 weeks. Hip BMD loss was greater for subjects on ADT (high-dose VITD: −1.5% vs placebo: −4.1%; p=0.03) than subjects on AI therapy (high-dose VITD: −0.2% vs placebo: −1.7%; p=0.02). Among the high-dose VITD group, there was no BMD difference at the total hip between those who received EXCAP exercise vs no EXCAP (p=0.96). The largest differences in BMD were for those with lower baseline VITD levels (&lt;27 ng/ml) for both total hip (high-dose VITD: −0.6% vs placebo: −3.2%; p&lt;0.001) and femoral neck (high-dose VITD: +0.2% vs placebo: −2.4%; p=0.03). No between-group pooled differences were noted for total spine BMD (high-dose VITD: −0.2% vs placebo: −0.1%; p=0.82). High-dose VITD increased serum VITD without negatively affecting serum calcium (Table). Conclusions: High-dose VITD was safe and effective in significantly reducing hip BMD loss, with the largest benefit in those with lower baseline VITD levels. A phase III RCT is needed to confirm these findings. NCI Funding: K07 CA168911/R21 CA175793/UG1 CA189961/T32 CA102618 Clinical trial information: NCT02064946, NCT01419730 . [Table: see text]

Circulating amino acids are associated with bone mineral density decline and ten-year major osteoporotic fracture risk in older community-dwelling adults.

With aging, poor bone mineral density (BMD) and accelerated decrease in BMD are strong risk factors for fracture. Reports of the associations of dietary protein intake with bone strength are inconsistent, possibly owing to differences in protein sources and amino acid (AA) composition. We examined the associations of serum AA with 4-year hip BMD loss and subsequent fracture risk within 10 years in older community-dwelling adults, and further addressed whether lifestyle, dietary protein intake and its source, and body composition would affect the associations. In 1424 men and 1573 women (mean age 72 years), using binary logistic regression, higher serum valine, leucine, isoleucine and tryptophan concentrations were associated (or approaching a borderline significance in case of the last three ones) with less hip BMD decline (defined as BMD loss ≥ 2.8 times the precision error of the BMD measurement at femoral neck) in 4 years later, with the OR (95%CI) /SD of AA increase, ranging from 0.83 (0.75, 0.91) to 0.92 (0.87, 0.98) after multiple adjustments for baseline age, gender, BMI, BMD, estimated glomerular filtration rate (eGFR), dietary protein intake (animal- and plant-derived protein intakes), calcium intake, established lifestyles (physical activity level, smoking and alcohol drinking status), osteoporosis medications, and changes of body fat and lean muscle mass. Higher serum total homocysteine (tHcy) concentration was independently associated with BMD decline 4 years later (OR (95%CI) /SD of 1.16 (1.05, 1.27)). Using multivariate Cox regression, higher serum tryptophan concentration potentially predicted low risk of incident major osteoporotic fractures (MOFs) (HR/SD (95%CI)=0.86 (0.75, 0.98)) after multiple adjustments. Higher serum tHcy was associated with MOFs (HR/SD (95%CI)=1.29 (1.12, 1.50)) risk after multiple adjustments in men. These findings suggest that a specific AA profile correlates with greater BMD and lower subsequent fracture risk, independent of diet and lifestyle factors.

Effect of Weight Change Following Intentional Weight Loss on Bone Health in Older Adults with Obesity.

This study aimed to examine change in bone mineral density (BMD) and trabecular bone score among older adult weight regainers (WR) and weight maintainers (WM). Observational data come from 77 older adults (meanage:67 [SD 5] years; 69% women; 70% white) with obesity (meanBMI: 33.6 [SD 3.7] kg/m2 ) who lost weight during an 18-month weight loss intervention. Total body mass and body composition, along with regional (total hip, femoral neck, lumbar spine) BMD and trabecular bone score, were measured at baseline, 18 months, and 30 months. WR (n = 36) and WM (n = 41) categories were defined as a ≥ 5% or < 5% weight gain from 18 to 30 months, respectively. Among skeletal indices, only total hip BMD was significantly reduced during the 18-month intervention period in both WRs (-3.9%; 95% CI: -5.8% to -2.0%) and WMs (-2.4%; 95% CI: -4.3% to -0.5%; P = 0.07). After adjustment for relevant baseline covariates and weight change from 0 to 18 months, 30-month change in total hip BMD was -2.6% (95% CI: -4.3% to -0.9%) and -3.9% (95% CI: -5.7% to -2.1%) among WRs and WMs, respectively (P = 0.07). Loss of hip BMD persists in the year after a weight loss intervention among older adults with obesity, regardless of weight regain status.

Psychosocial stress and bone loss among postmenopausal women: results from the Women’s Health Initiative

BackgroundBone loss is a major public health concern with large proportions of older women experiencing osteoporotic fractures. Previous research has established a relationship between psychosocial stressors and fractures. However, few...

A phase II RCT of high-dose vitamin D supplementation and exercise for cancer treatment-induced bone loss in breast cancer patients on aromatase inhibitors.

11500 Background: Cancer-treatment-induced bone loss (CTIBL) is a side effect of aromatase inhibitors (AIs) and can result in osteoporotic fractures. Vitamin D (VITD) protects against postmenopausal bone loss but it is unclear if the recommended daily allowance (RDA: 600 IU/day) of VITD is sufficient to prevent CTIBL. This phase II RCT aimed to assess the feasibility, safety, and preliminary efficacy of high-dose VITD (with and without exercise) on bone mineral density (BMD) compared to the RDA. Methods: Non-metastatic breast cancer patients starting AIs with low VITD (&lt;32 ng/ml) were randomized 1:1:1 into 3 arms: 1) placebo 2) high-dose VITD (50,000 IU/week) or 3) high-dose VITD + Exercise for Cancer Patients (EXCAP): a home-based, personalized walking and resistance band training program for 24 weeks. All subjects received the RDA of VITD 600 IU/day. Serum VITD and calcium levels were assessed at baseline, weeks 6, 12, 18, and 24. BMD was assessed at the hip via DXA at baseline and week 24. Results: Of the 116 subjects randomized (mean age = 60; 94% white; mean baseline VITD = 24.6 ng/mL), 90 provided fully evaluable data. Compliance (≥ 80% of instructed doses) exceeded 95% in all 3 arms with no between-group difference. ANCOVA showed significant differences between groups on final VITD levels (high-dose = 63.6 vs high-dose + EXCAP = 60.3 vs placebo = 32.0 ng/mL; p&lt;0.001) without severe calcium toxicities, as indicated by final calcium level (high-dose = 9.4 vs high-dose + EXCAP = 9.5 vs placebo = 9.4 ng/mL; p = 0.78). The placebo group lost a significant amount of hip BMD (−1.7%; p &lt; 0.01) while hip BMD was maintained in the high-dose (−0.1%; p = 0.77) and high-dose + EXCAP (−0.2%; p = 0.74) resulting in significant between-group differences for high-dose + EXCAP vs placebo (p = 0.04) and high-dose vs placebo (p = 0.05). Conclusions: This is one of the first studies to show our novel high-dose VITD intervention, with and without exercise, significantly reduced hip BMD loss in breast cancer patients on AIs. Moreover, high-dose VITD supplementation is safe and feasible in this population. A phase III RCT is needed to confirm these findings. Funding: K07CA168911. Clinical trial information: NCT01419730.

Effects of a falls exercise intervention on strength, power, functional ability and bone in older frequent fallers: FaME (Falls Management Exercise) RCT secondary analysis.

Objectives:Falls Management Exercise (FaME) has been shown to reduce falls in frequent fallers and in lower risk sedentary older people. The effects of FaME on the strength, power, physical function and bone health of frequently falling older women are yet to be established.Methods:This paper reports secondary analysis of data from the original randomised controlled trial of FaME in 100 community dwelling women aged ≥65 years with a history of ≥3 falls in the previous year. Intervention was group delivered, weekly one hour tailored dynamic balance and strength exercise classes and home exercise for nine months.Outcome measures included:strength (handgrip, quadriceps, hamstrings, hip abductors, ankles), lower limb explosive power and functional tests (timed up and go, functional reach, timed floor rise and balance), analysed using Linear Mixed Model analysis. Bone Mineral Density (BMD) at hip and spine was measured in a smaller sub-group and analysed using t-tests.Results:Significant time*group interactions in all measures of strength, except isometric ankle dorsiflexion, concentric hamstring and eccentric quadriceps strength. These improvements in strength equated to average improvements of 7-45%. There were also significant improvements in explosive power (W/kg) (18%, p=0.000), timed up and go (16%, p=0.000), functional reach (17%, p=0.000), floor rise (10%, p=0.002) and eyes closed static balance (56%, p=0.000). There was a significant loss of hip BMD in the control group (neck of femur p<0.05; ward’s triangle p<0.02).Conclusion:The FaME intervention improves lower limb strength, power and clinically relevant functional outcomes in frequently falling older women.

Incident fracture is associated with a period of accelerated loss of hip BMD: the Study of Osteoporotic Fractures.

A prior fracture is one of the strongest predictors of subsequent fracture risk, but the etiology of this phenomenon remains unclear. Systemic bone loss post-fracture could contribute to increased risk of subsequent fractures. Therefore, in this study, we investigated whether incident fractures, including those distant to the hip, are associated with accelerated loss of hip bone mineral density (BMD) in elderly women. We analyzed data from 3956 Caucasian women aged ≥ 65years who were enrolled in the Study of Osteoporotic Fractures and completed hip BMD measurements at study visit 4 (year 6) and visit 6 (year 10). Clinical fractures between visits 4 and 6 were ascertained from triannual questionnaires and centrally adjudicated by review of community radiographic reports. Subjects provided questionnaire information and clinical variables at examinations for known and potential covariates. Generalized linear models were used to calculate average annual percent change in total hip BMD between visits 4 and 6 for each incident fracture type and for upper body and lower body fractures combined. A subset of women (n = 3783) was analyzed for annual total hip BMD change between study visits 4 and 5 and between study visits 5 and 6 to evaluate change in total hip BMD during these 2-year intervals. Women with incident upper body fracture or incident lower body fracture exhibited reductions in total hip BMD of 0.89 and 0.77% per year, respectively, while women who did not fracture exhibited reductions in total hip BMD of 0.66% per year during the 4-year period. Accelerated loss of hip BMD was isolated to the 2-year time interval that included the fracture. Loss of total hip BMD was not affected by the number of days from fracture to follow up DXA. Systemic bone loss following fracture may increase the risk of future fractures at all skeletal sites. There is a need for improved understanding of mechanisms leading to apparent accelerated bone loss following a fracture in order to reduce subsequent fracture risk.

Brief Report: Changes in Plasma RANKL-Osteoprotegerin in a Prospective, Randomized Clinical Trial of Initial Antiviral Therapy: A5260s.

The contributions of the receptor activator of nuclear factor kappa-B ligand (RANKL)/osteoprotegerin (OPG) axis to cardiovascular and bone disease in treated HIV-1 infection are not well defined. Prospective, observational, longitudinal study. In a subset analysis of a prospective randomized clinical trial, 234 HIV-1-infected antiretroviral therapy-naive participants received tenofovir-emtricitabine plus either atazanavir/ritonavir, darunavir/ritonavir, or raltegravir and achieved plasma HIV-1 RNA <50 copies per milliliter by week 24 and thereafter. Associations between plasma RANKL, OPG, or RANKL/OPG ratio levels with total, hip, and spine bone mineral density (BMD) loss or progression of carotid artery intima-media thickness were assessed longitudinally over 96 weeks. Over 96 weeks, all treatment groups had similar and sustained declines in plasma RANKL, increases in plasma OPG, and subsequently, decreases in the RANKL/OPG ratio. There were no associations between plasma RANKL or RANKL/OPG ratio levels with total, hip, and spine BMD loss or progression of carotid artery intima-media thickness; however, plasma OPG in successfully treated HIV-infected patients (week 48 and 96) was associated with spine BMD loss. In virologically suppressed HIV-infected patients, the evolution of bone disease could be linked to plasma OPG levels; however, the role of plasma levels of RANKL and RANKL/OPG ratio in the prediction of morbidity in treated HIV-1 infection may be limited.

Radiographic Emphysema, Circulating Bone Biomarkers, and Progressive Bone Mineral Density Loss in Smokers.

Osteoporosis is common in individuals with chronic obstructive pulmonary disease. Lung-specific factors, including radiographic emphysema, independently associate with low bone mineral density in cross-sectional smoking cohorts. However, factors associated with progressive bone loss in smokers are understudied and largely unknown. To determine the relationship between radiographic emphysema, circulating bone metabolism markers, and pulmonary function and accelerated bone mineral density loss in smokers. Two hundred and forty male and female current and former smokers, 40 years of age or older, underwent baseline and 2-year assessments of pulmonary function, computed tomography-assessed emphysema, dual X-ray absorptiometry-measured bone mineral density, and circulating bone metabolism biomarker levels (type I collagen C-telopeptide [CTX], amino-terminal propeptide of type I procollagen [P1NP]). The association of radiographic emphysema, bone metabolism biomarker levels, and pulmonary function with accelerated hip bone mineral density loss, defined by the 75th percentile of annual hip bone mineral density decline, was determined by logistic regression modeling with adjustment for age, sex, inhaled and intermittent steroid use, active smoking, body mass index, and the presence of baseline low hip bone mineral density. Of those participants with accelerated hip bone mineral density loss, 22% had moderate or severe visually assessed emphysema compared with 7.2% of smokers without accelerated bone mineral density decline. Moderate to severe visually assessed emphysema (odds ratio, 2.84; 95% confidence interval, 1.01-7.98 compared with trace/mild or no visually assessed emphysema) and the 75th percentile of CTX levels (odds ratio, 2.38; 95% confidence interval, 1.20-4.72 compared with CTX levels below the 75th percentile), a marker of bone resorption, were associated with accelerated hip bone mineral density decline after adjustment for covariates and the presence of baseline low hip bone mineral density. FEV1% predicted was not associated with accelerated bone mineral density decline after adjustment for covariates. Multivariate modeling showed moderate to severe visually assessed emphysema, and the 75th percentiles of CTX were independently associated with accelerated hip bone mineral density decline after adjustment for covariates. Emphysema and elevated markers of bone resorption are independently associated with progressive bone mineral density loss in smokers. These clinical markers may guide targeted bone mineral density screening and monitoring in smokers at highest risk.