Change In Hip Bone Mineral Density Research Articles

Chemokine CXCL9, a marker of inflammaging, is associated with changes of muscle strength and mortality in older men

SummaryOur study examined associations of the CXC motif chemokine ligand 9 (CXCL9), a pro-inflammatory protein implicated in age-related inflammation, with musculoskeletal function in elderly men. We found in certain outcomes both cross-sectional and longitudinal significant associations of CXCL9 with poorer musculoskeletal function and increased mortality in older men. This requires further investigation.PurposeWe aim to determine the relationship of (CXCL9), a pro-inflammatory protein implicated in age-related inflammation, with both cross-sectional and longitudinal musculoskeletal outcomes and mortality in older men.MethodsA random sample from the Osteoporotic Fractures in Men (MrOS) Study cohort (N = 300) was chosen for study subjects that had attended the third and fourth clinic visits, and data was available for major musculoskeletal outcomes (6 m walking speed, chair stands), hip bone mineral density (BMD), major osteoporotic fracture, mortality, and serum inflammatory markers. Serum levels of CXCL9 were measured by ELISA, and the associations with musculoskeletal outcomes were assessed by linear regression and fractures and mortality with Cox proportional hazards models.ResultsThe mean CXCL9 level of study participants (79.1 ± 5.3 years) was 196.9 ± 135.2 pg/ml. There were significant differences for 6 m walking speed, chair stands, physical activity scores, and history of falls in the past year across the quartiles of CXCL9. However, higher CXCL9 was only significantly associated with changes in chair stands (β = − 1.098, p < 0.001) even after adjustment for multiple covariates. No significant associations were observed between CXCL9 and major osteoporotic fracture or hip BMD changes. The risk of mortality increased with increasing CXCL9 (hazard ratio quartile (Q)4 vs Q1 1.98, 95% confidence interval 1.25–3.14; p for trend < 0.001).ConclusionsGreater serum levels of CXCL9 were significantly associated with a decline in chair stands and increased mortality. Additional studies with a larger sample size are needed to confirm our findings.

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.

OR13-06 Romosozumab After Denosumab Improves Lumbar Spine Bone Mineral Density And Microarchitecture Greater Than Denosumab Continuation In Postmenopausal Women

Abstract Disclosure: N. Hong: None. S. Shin: None. H. Kim: None. Y. Rhee: None. Transitioning to romosozumab from antiresorptives can be an effective strategy to improve bone strength. A phase 2 trial and a few observational studies showed improvement of lumbar spine bone mineral density (BMD) with maintained hip bone density by romosozumab after denosumab. However, whether transition to romosozumab after denosumab is associated with greater improvement in BMD and microarchitecture compared to denosumab continuation remains unclear. In this propensity score-matched cohort study, we analyzed data from postmenopausal women who initiated denosumab between 2017 and 2020 (at least two injections; n=696). Individuals who were transited to 12 months of romosozumab after denosumab (n=105) were 1:1 matched to those who continued denosumab (n=591) by propensity score using age (69 years), body mass index, BMD, and numbers of denosumab injection at the time of transition, BMD improvement during denosumab treatment, prior fracture and bisphosphonate use (n=93 for each; denosumab-romosozumab [DR] and denosumab-denosumab [DD]). BMD gain by denosumab in DR and DD groups from denosumab initiation to transition time (to romosozumab or denosumab continuation; median 4 times [range 2 to 8] of denosumab injection) was +4.6% and +2.4% in the lumbar spine (LS, T-score −3.4 to −3.1) and total hip (TH, T-score −2.5 to −2.4), without statistical difference. DR group showed greater LSBMD gain compared to the DD (+7.0% vs. +2.5%, P&amp;lt;0.001) during 12 months after the transition time, yielding greater net LSBMD gain in DR (median 2 years of denosumab followed by 1-year romosozumab) compared to DD (median 3 years of denosumab; +11.6% vs. +7.0%, P&amp;lt;0.001). Differences in LSBMD gain between DR and DD groups remained robust (adjusted difference +4.7% point, P&amp;lt;0.001) after adjustment for covariates. Hip BMD changes did not differ between DR and DD (DR vs. DD; FN, +1.3% vs. +2.0%, p=0.409; TH, -0.9% vs. +0.2%, P=0.132). DR group showed significant improvement in the trabecular bone score during romosozumab use (1.288 to 1.311, p=0.005), whereas denosumab continuation in the DD group did not (1.297 to 1.309, p=0.103). During 12 months, one incident morphometric vertebral fracture (grade 1) and one nonvertebral fracture (patella) were observed in DD, whereas one ankle fracture was observed in the DR group. In summary, romosozumab after denosumab improved lumbar spine BMD and microarchitecture greater than denosumab continuation, with the maintenance of hip BMD. Presentation: Friday, June 16, 2023

Simplification from tenofovir disoproxil fumarate plus lamivudine or emtricitabine plus ritonavir-boosted protease inhibitor to ritonavir-boosted atazanavir plus lamivudine in virologically suppressed HIV-infected adults with osteopenia: a pilot study.

Tenofovir disoproxil fumarate, particularly when given with a ritonavir-boosted PI, reduces bone mineral density (BMD) and increases bone turnover markers (BTMs). Ritonavir-boosted atazanavir plus lamivudine is a feasible simplified option. We evaluated whether switching from a triple ritonavir-boosted PI plus tenofovir disoproxil fumarate to a two-drug regimen of lamivudine plus ritonavir-boosted atazanavir would improve BMD. Single-arm pilot study. Virologically suppressed patients on tenofovir disoproxil fumarate plus lamivudine or emtricitabine plus ritonavir-boosted PI with low BMD, without previous resistance mutations and/or virological failure to study drugs were switched to 100/300 mg of ritonavir-boosted atazanavir plus 300 mg of lamivudine once daily. The primary endpoint was BMD change by DXA at Week 48. There were 31 patients, 4 (13%) female, and median age was 40 years. Seven participants (22.5%) had osteoporosis. At 48 weeks, mean (SD) changes in spine and hip BMD were +0.01 (0.03) (P = 0.0239) and +0.013 (0.03) g/cm2 (P = 0.0046), respectively. Mean (SD) T-score changes were +0.1 (0.23) (P = 0.0089) and +0.25 (0.76) (P = 0.0197), respectively. N-telopeptide and urine tenofovir disoproxil fumarate toxicity markers showed significant improvements. One participant withdrew from the study and two were lost to follow-up. There were no virological failures, or serious or grade 3-4 adverse events. Switching from a tenofovir disoproxil fumarate plus ritonavir-boosted PI triple therapy to a lamivudine plus ritonavir-boosted atazanavir two-drug regimen in virologically suppressed HIV-infected adults with low BMD was safe, increased low BMD and reduced plasma markers of bone turnover and urine markers of tenofovir disoproxil fumarate toxicity over 48 weeks.

Changes in Bone Mineral Density and Trabecular Bone Score over Time between Vegetarian and Non-Vegetarian Middle-Aged and Older Women: A Three-Year Retrospective Medical Record Review.

The effect of a vegetarian diet on bone health remains controversial. This retrospective medical record review compared changes in bone mineral density (BMD) and trabecular bone score (TBS) between vegetarian and non-vegetarian middle-aged and older women who underwent two general health examinations (T1 and T2) that were approximately three years apart. Generalized estimating equations were used to compare the change in lumbar spine and bilateral hip BMD and TBS over time. At T1, the mean age of the patients was 56.6 years (standard deviation 9.7 years) and the mean interval between T1 and T2 was 2.7 years. For women aged 40–55 years, compared with non-vegetarians, vegetarians were significantly associated with a larger reduction in lumbar spine BMD (p < 0.001) and left hip femoral neck BMD (p = 0.015) over the three-year interval. On the contrary, changes in BMD were not significant at any site in women aged ≥ 56 years. Moreover, the changes in BMD and TBS over the three-year interval did not significantly differ between vegetarian and non-vegetarian women aged 65–90 years. In conclusion, for women aged 40–55 years, vegetarian diets reduced bone quantity, as measured by BMD, but not bone quality, as measured by TBS.

Bone mass measurement by DXA should be interpreted with caution in the CKD population with vascular calcification

BackgroundKDIGO guidelines suggest the use of dual-energy X-ray absorptiometry (DXA) to assess bone mineral density (BMD) in patients with CKD 3a-5D. Previous studies have demonstrated an association between trabecular bone mass loss and coronary artery calcification (CAC) progression. This study aimed to prospectively investigate the relationship between BMD changes, quantified by DXA, and CAC progression in the non-dialyzed CKD population. MethodsIn this post hoc study, BMD by DXA was measured at the lumbar spine and total hip at baseline and 12-months. Patients were categorized according to BMD changes into 3 different groups: LOSS, UNCHANGED and GAIN. CAC quantification was obtained by multislice computed tomography at baseline and 12-months. Results87 patients (55.6 ± 10.7 years, 62% males, 30% diabetic, eGFR = 39.2 ± 18.1 mL/min/1.73m2) were enrolled. CAC was found in 41 (47%) of the patients at baseline and CAC progression in 25 (64%) of them. Considering the lumbar spine and total hip BMD changes together, 24%, 48%, and 25% of the patients were in the LOSS, UNCHANGED and GAIN groups, respectively. Compared to the UNCHANGED or LOSS groups, the GAIN group had an increase in calcium score (p = 0.04) and a higher proportion of patients with CAC progression (p = 0.01). In the logistic regression analysis, CAC progression was 4.5 times more likely to be in the GAIN group. ConclusionsThe association between the increase in BMD values and the progression of vascular calcification was the result of two concomitant processes overlapping, leading to a misinterpretation of DXA results. Thus, the use of DXA for the evaluation of bone mass, especially at the lumbar spine, must be applied with restraint and its results very carefully interpreted in CKD patients.

Does Bisphosphonate Increase the Sclerosis of Tibial Subchondral Bone in the Progression of Knee Osteoarthritis-A Propensity Score Matching Cohort Study Based on Osteoarthritis Initiative.

Bisphosphonate has great potential in KOA therapy, but whether the anti-resorption mechanism of bisphosphonate aggravates sclerosis of subchondral bone remains unclear. We found that bisphosphonate use did not increase sclerosis of subchondral bone in established KOA, perhaps resolving some concerns about bisphosphonate in patients with KOA.Introduction: Most studies have focused on the protective effect of bisphosphonate on early knee osteoarthritis (KOA) through its anti-resorption mechanism in osteoclasts. However, late KOA has a decreased rate of resorption, which is the opposite of early KOA. The risk of subchondral bone sclerosis in late KOA after using bisphosphonate has not been investigated using morphometry.Methods: Forty-five patients who had ever used bisphosphonate (or 33 patients with current use) were matched with controls through propensity matching methods, including age, body mass index (BMI), sex, health status (12-Item Short Form Survey physical health score), physical activity level (Physical Activity Scale for the Elderly score), vitamin D use, and calcium use. At the baseline and 12-month (or 18-month) follow-up, bone mineral density (BMD) of the tibia and hip was measured by dual-energy X-ray absorptiometry (DXA), and medial tibial subchondral bone morphometry: bone volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), and trabecular separation (Tb.Sp) were calculated based on 3-T trabecular MRI. Data were obtained from the Bone Ancillary Study in the Osteoarthritis Initiative (OAI) project.Results: The yearly percentage change in hip BMD of the current bisphosphonate-use group was significantly greater than that of the non-bisphosphonate-use group (0.7% vs. −1%, P = 0.02). The other outcomes (BV/TV, Tb.N, Tb.Sp, Tb.Th, tibia medial BMD, and tibia lateral BMD) between the two groups presented no significant difference. The non-bisphosphonate-use group experienced a significant increase in Tb.Th [2%, 95% CI = (1%, 4%), P = 0.01], while the bisphosphonate-use group presented no significant change [1%, 95% CI = (−2%, 4%), P = 0.54].Conclusions: Bisphosphonate use did not increase sclerosis of subchondral bone in established KOA. Bisphosphonate might have a stage-dependent effect on subchondral bone in KOA initiation and progression.

Bone changes with candidate PrEP regimens containing tenofovir disoproxil fumarate and/or maraviroc and/or emtricitabine in US men and women: HPTN 069/ACTG A5305.

Tenofovir disoproxil fumarate-containing pre-exposure prophylaxis (PrEP) has been associated with decreases in bone mineral density (BMD), but the bone effects of other non-tenofovir disoproxil fumarate candidate PrEP regimens are not well described. The HPTN 069/ACTG A5305 study randomized 406 US cisgender men and transgender women, and 188 cisgender women at risk for HIV infection to one of four double-blinded regimens: (i) maraviroc; (ii) maraviroc + emtricitabine; (iii) maraviroc + tenofovir disoproxil fumarate; or (iv) tenofovir disoproxil fumarate + emtricitabine. BMD was measured in a subset of participants at the lumbar spine (LS) and hip by dual-energy X-ray absorptiometry (DXA) at baseline and 48 weeks. Percentage change in LS and hip BMD was compared between the tenofovir disoproxil fumarate- and non-tenofovir disoproxil fumarate-containing arms by Wilcoxon rank-sum tests and multiple linear regression adjusting for sex, race and baseline BMI. At baseline (n = 307), the median age was 33 years, 56% male and 43% black. At the hip, the median percentage change in BMD at 48 weeks was -1.05% in the tenofovir disoproxil fumarate arms and 0.0% in the non-tenofovir disoproxil fumarate arms (between group P = 0.001). No interaction by sex was observed. The median percentage change in LS BMD was not different between arms. Tenofovir disoproxil fumarate-containing PrEP was associated with significantly greater bone loss compared with maraviroc ± emtricitabine PrEP at the hip, but not the LS. The BMD changes at the hip were similar in magnitude in men and women.

Circulating miR-122-5p and miR-375 as Potential Biomarkers for Bone Mass Recovery after Parathyroidectomy in Patients with Primary Hyperparathyroidism: A Proof-of-Concept Study.

Primary hyperparathyroidism (PHPT) is the leading cause of secondary osteoporosis. Although bone mineral density (BMD) tends to recover after parathyroidectomy in PHPT patients, the degree of recovery varies. Circulating microRNAs (miRNAs) profiles are known to be correlated with osteoporosis and fracture. We aimed to investigate whether osteoporotic fracture-related miRNAs are associated with postoperative BMD recovery in PHPT. Here, 16 previously identified osteoporotic fracture-related miRNAs were selected. We analyzed the association between the preoperative level of each miRNA and total hip (TH) BMD change. All 12 patients (among the 18 patients enrolled) were cured of PHPT after parathyroidectomy as parathyroid hormone (PTH) and calcium levels were restored to the normal range. Preoperative miR-19b-3p, miR-122-5p, and miR-375 showed a negative association with the percent changes in TH BMD from baseline. The association remained robust for miR-122-5p and miR-375 even after adjusting for sex, age, PTH, and procollagen type 1 N-terminal propeptide levels in a multivariable model. In conclusion, preoperative circulating miR-122-5p and miR-375 levels were negatively associated with TH BMD changes after parathyroidectomy in PHPT patients. miRNAs have the potential to serve as predictive biomarkers of treatment response in PHPT patients, which merits further investigation.

Long-term particulate matter exposure and bone mineral density in the Women’s Health Initiative

BACKGROUND AND AIM: Ambient particulate matter air pollution 10 μm (PM10) concentrations have been associated with several outcomes, but few studies have examined their association with bone mineral density (BMD). Previous studies have suggested an effect of air pollution on bone health, but none has evaluated its impact in postmenopausal women. METHODS: We studied the longitudinal PM10-BMD association among 5,080 postmenopausal women in the Women’s Health Initiative Clinical Trials (WHI-CT). We used log-normal, ordinary kriging to estimate daily mean PM10 concentrations (μg/m3) at geocoded participant addresses. We averaged the means over 1-, 3-, and 5-year periods before triennial, dual energy X-ray absorptiometry (DXA) exams. We estimated total hip, lumbar spine, and total body BMD (in g/cm2) and their corresponding T-scores. We estimated the association of PM10 with BMD and T-scores using multivariable linear mixed models while controlling for correlation of repeated measures among participants and adjusting for age at DXA, race/ethnicity, income, body mass index (kg/m2), smoking status, coffee consumption, physical activity, CT randomization arm, US region of residence, and DXA equipment serial number. Multiple imputation was done for missing data. RESULTS:At baseline, women were aged 50-79 years, 78% were White, 40% were college graduates, and 71% earned $40,000/year. PM10 concentrations at baseline were cross-sectionally associated with both hip, lumbar spine, and whole-body BMD and T-scores (p 0.05). Longitudinally, lumbar spine BMD decreased 0.052 (95% confidence interval [95%CI]: 0.067, 0.037) g/cm2/year per 10% (2.21 ug/m3) increase in 5-year mean PM10 concentration. Lumbar spine T-scores also decreased with increasing duration of the 3- and 5-year mean PM10 concentrations: -0.362 Standard Deviations (SD) (-0.490, -0.235) and -0.512 SD (-0.649, -0.375), respectively. No association was seen with changes in hip or total body BMD. CONCLUSIONS:This is the first study suggesting an inverse association of ambient PM10 with BMD among postmenopausal women. KEYWORDS: Air pollution, long-term, PM10, bone mineral density, t-score, osteoporosis.

Integrative analysis of genetic and clinical risk factors for bone loss in a Korean population.

The relative contribution of genetic and clinical factors for bone loss is not well known. This study aimed to investigate the annualized percentage change in total hip bone mineral density (BMD) and the genetic and clinical risk factors for bone loss in a Korean prospective cohort study over a 6-year period. We included 645 men aged ≥50years and 683 postmenopausal women who had repeated BMD testing between 2007 and 2014. The association between covariates and annualized percentage change in hip BMD was analyzed through the multivariate linear regression analysis. A total of 2614 single-nucleotide polymorphisms (SNPs) from 23 known BMD-related candidate genes and genome-wise association study were investigated. Hip bone loss increased more rapidly in women than in men with advancing age. Hip bone loss in men increased with lean mass (LM) loss (%/year) (P<0.001) and current smoking (P=0.024) and decreased with increasing waist circumference (WC) (P<0.001), alcohol consumption (P=0.049), and increase in red blood cell counts (P=0.031). Decreasing WC (P=0.009), LM loss (%/year) (P<0.001), and years since menopause ≤ 3years (P=0.003) significantly correlated with hip bone loss in women aged 45-59years. Hip bone loss in women aged ≥60years increased with advancing age (P=0.012), alcohol consumption (P=0.028), LM loss (%/year) (P=0.031), and fat mass loss (%/year) (P<0.001) and decreased with increasing WC (P=0.025). LRP5 rs498830 (β=0.127, P=0.007) and TNFSF11 rs7325635 (β=0.146, P=0.001) were the top SNPs related to hip bone loss in men and postmenopausal women, respectively. However, none of the SNPs were associated with hip bone loss after Benjamini-Hochberg adjustment. In this study, decreasing WC and LM were significant risk factors for hip bone loss in both men and women. Those factors were also identified that had sex-specific or age-specific effects on hip bone loss. None of the SNPs were associated with hip bone loss after multiple testing adjustments. The understanding of the modifiable factors contributing to bone loss has been broadened, and this may have implications such as in developing individualized preventive strategy. Further studies are needed to better predict the risk for bone loss in men and women.

Contributions of Clinical and Technical Factors to Longitudinal Change in Trabecular Bone Score and Bone Density: A Registry-Based Individual-Level Analysis.

Lumbar spine trabecular bone score (TBS), a gray-level texture measure derived from spine dual-energy X-ray absorptiometry (DXA) images, is a bone mineral density (BMD)-independent risk factor for fracture. An unresolved question is whether TBS is sufficiently responsive to change over time or in response to widely used osteoporosis therapy at the individual level to serve as a useful biomarker. Using the Manitoba DXA Registry, we identified 11,643 individuals age 40 years and older with two fan-beam DXA scans performed on the same instrument within 5 years (mean interval 3.2 years), of whom 6985 (60.0%) received antiresorptive osteoporosis medication (majority oral bisphosphonate) between the scans. We examined factors that were associated with a change in lumbar spine TBS, lumbar spine BMD, and total hip BMD exceeding the 95% least significant change (LSC). Change exceeding the LSC was identified in 23.0% (9.3% increase, 13.8% decrease) of lumbar spine TBS, 38.2% (22.1% increase, 16.1% decrease) lumbar spine BMD, and 42.5% (17.6% increase, 24.9% decrease) total hip BMD measurement pairs. From regression models, the variables most strongly associated with significant change in TBS (decreasing order) were tissue thickness change, acquisition mode change, weight change, and spine percent fat change. Consistent with the insensitivity of TBS to oral antiresorptive therapies, use of these agents showed very little effect on TBS change. In contrast, for both spine BMD change and total hip BMD change, osteoporosis medication use was the most significant variable, whereas tissue thickness change, acquisition mode change, and weight change had relatively weak effects. In summary, change in spine TBS using the present algorithm appears to be strongly affected by technical factors. This suggests a limited role, if any, for using TBS change in untreated individuals or for monitoring response to antiresorptive treatment in routine clinical practice with the current version of the TBS algorithm. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Treatment-related changes in bone mineral density as a surrogate biomarker for fracture risk reduction: meta-regression analyses of individual patient data from multiple randomised controlled trials

The validation of bone mineral density (BMD) as a surrogate outcome for fracture would allow the size of future randomised controlled osteoporosis registration trials to be reduced. We aimed to determine the association between treatment-related changes in BMD, assessed by dual-energy x-ray absorptiometry, and fracture outcomes, including the proportion of treatment effect explained by BMD changes. We did a pooled analysis of individual patient data from multiple randomised placebo-controlled clinical trials. We included data from multicentre, randomised, placebo-controlled, double-blind trials of osteoporosis medications that included women and men at increased osteoporotic fracture risk. Using individual patient data for each trial we calculated mean 24-month BMD percent change together with fracture reductions and did a meta-regression of the association between treatment-related differences in BMD changes (percentage difference, active minus placebo) and fracture risk reduction. We also used individual patient data to determine the proportion of anti-fracture treatment effect explained by BMD changes and the BMD change needed in future trials to ensure fracture reduction efficacy. Individual patient data from 91 779 participants of 23 randomised, placebo-controlled trials were included. The trials had 1-9 years of follow-up and included 12 trials of bisphosphonate, one of odanacatib, two of hormone therapy (one of conjugated equine oestrogen and one of conjugated equine oestrogen plus medroxyprogesterone acetate), three of PTH receptor agonists, one of denosumab, and four of selective oestrogen receptor modulator trials. The meta-regression revealed significant associations between treatment-related changes in hip, femoral neck, and spine BMD and reductions in vertebral (r2 0·73, p<0·0001; 0·59, p=0·0005; 0·61, p=0·0003), hip (0·41, p=0·014; 0·41, p=0·0074; 0·34, p=0·023) and non-vertebral fractures (0·53, p=0·0021; 0·65, p<0·0001; 0·51, p=0·0019). Minimum 24-month percentage changes in total hip BMD providing almost certain fracture reductions in future trials ranged from 1·42% to 3·18%, depending on fracture site. Hip BMD changes explained substantial proportions (44-67%) of treatment-related fracture risk reduction. Treatment-related BMD changes are strongly associated with fracture reductions across randomised trials of osteoporosis therapies with differing mechanisms of action. These analyses support BMD as a surrogate outcome for fracture outcomes in future randomised trials of new osteoporosis therapies and provide an important demonstration of the value of public access to individual patient data from multiple trials. Foundation for National Institutes of Health.

Effects of High-Intensity Resistance Training on Osteopenia and Sarcopenia Parameters in Older Men with Osteosarcopenia-One-Year Results of the Randomized Controlled Franconian Osteopenia and Sarcopenia Trial (FrOST).

Dynamic resistance exercise (DRT) might be the most promising agent for fighting sarcopenia in older people. However, the positive effect of DRT on osteopenia/osteoporosis in men has still to be confirmed. To evaluate the effect of low-volume/high-intensity (HIT)-DRT on bone mineral density (BMD) and skeletal muscle mass index (SMI) in men with osteosarcopenia, we initiated the Franconian Osteopenia and Sarcopenia Trial (FrOST). Forty-three sedentary community-dwelling older men (aged 73 to 91 years) with osteopenia/osteoporosis and SMI-based sarcopenia were randomly assigned to a HIT-RT exercise group (EG; n = 21) or a control group (CG; n = 22). HIT-RT provided a progressive, periodized single-set DRT on machines with high intensity, effort, and velocity twice a week, while CG maintained their lifestyle. Both groups were adequately supplemented with whey protein, vitamin D, and calcium. Primary study endpoint was integral lumbar spine (LS) BMD as determined by quantitative computed tomography. Core secondary study endpoint was SMI as determined by dual-energy X-ray absorptiometry. Additional study endpoints were BMD at the total hip and maximum isokinetic hip-/leg-extensor strength (leg press). After 12 months of exercise, LS-BMD was maintained in the EG and decreased significantly in the CG, resulting in significant between-group differences (p < 0.001; standardized mean difference [SMD] = 0.90). In parallel, SMI increased significantly in the EG and decreased significantly in the CG (p < 0.001; SMD = 1.95). Total hip BMD changes did not differ significantly between the groups (p = 0.064; SMD = 0.65), whereas changes in maximum hip-/leg-extensor strength were much more prominent (p < 0.001; SMD = 1.92) in the EG. Considering dropout (n = 2), attendance rate (95%), and unintended side effects/injuries (n = 0), we believe our HIT-RT protocol to be feasible, attractive, and safe. In summary, we conclude that our combined low-threshold HIT-RT/protein/vitamin D/calcium intervention was feasible, safe, and effective for tackling sarcopenia and osteopenia/osteoporosis in older men with osteosarcopenia. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

Efficacy of zoledronic acid in older prostate cancer patients undergoing androgen deprivation therapy

ObjectivesThe purpose of this study is to evaluate the efficacy of annual zoledronic acid treatment in Japanese patients with nonmetastatic prostate cancer during androgen deprivation therapy (ADT). MethodsThis is a single institution 12-month study. Between 2016 and 2019, patients aged 70 years or older on ADT for nonmetastatic prostate cancer had bone mineral density (BMD) measured and 10-year probability of fracture calculated using fracture risk assessment tool (FRAX). Patients who showed osteopenia or had a 10-year hip fracture risk ≥ 3% or a 10-year probability of major osteoporotic fracture ≥ 20% were offered treatment with zoledronic acid 5 mg intravenously (ZA group). The patients who did not receive treatment were set as the control group. Lumbar and hip BMD were measured 6 and 12 months after treatment in the ZA group and 12 months after baseline in the control group. The yearly BMD change of both groups was compared. ResultsThe mean ages of the ZA group (n = 26) and control group (n = 12) were 80.5 ± 9.1 and 76.1 ± 6.7 years, respectively. In the ZA group, lumbar and hip BMD changes at 12 months were +2.1% and +0.8%, respectively. In the control group, lumbar and hip BMD changes were −0.9% and −4.9%, respectively. There were statistically significant differences between the 2 groups in BMD percent changes (P < 0.05). ConclusionsWithout intervention, BMD tends to continue to decrease during ADT. Our findings suggest that administration of zoledronic acid enables maintenance of BMD in the older adults.

Long-Term Impact of Calcium and Vitamin D Supplementation on Bone Density in HIV+ Patients with Documented Deficiencies.

To assess the efficacy of long-term calcium and vitamin D treatment on bone mineral density (BMD) in HIV+ patients on combined antiretroviral therapy (cART). A retrospective, single-center cohort study. Between March 2010 and July 2012, 268 HIV+ patients were screened for vitamin D and calcium deficiency. Those with proven vitamin D or calcium deficiency received supplementation according to a predefined protocol, and were offered further evaluation of BMD by dual-energy X-ray absorptiometry (DEXA). Calcium and vitamin D status and BMD were assessed at baseline (T0) and approximately one (T1) and 4-6 years (T2) later. Percentual change in BMD of the lumbar spine and hip was compared with reported rates of change in HIV+ patients on cART without standard calcium and vitamin D treatment. The prevalence of vitamin D deficiency and calcium deficiency was 46% and 43%, respectively. Thirteen percent of patients had secondary hyperparathyroidism at baseline. DEXA performed in patients with a deficiency revealed osteopenia in 40% and osteoporosis in 8% of patients. The expected long-term change in lumbar spine and hip BMDs at T2 was -0.7%, -1.5%, and -1.5%, respectively. The measured changes were +2.3%, -0.6%, and -0.6%, respectively. The difference between measured and expected rate of change was significant for the lumbar spine (3.0%, p < .05), but not for the hip. Long-term vitamin D and calcium supplementation improves lumbar spine BMD of HIV+ patients with osteopenia or osteoporosis and with proven calcium and/or vitamin D deficiencies. Screening and treatment are recommended to become part of regular care.

Prolonged Effect of Zoledronic Acid on Bone Mineral Density and Turnover in HIV-Infected Adults on Tenofovir: A Randomized, Open-Label Study.

Zoledronic acid (ZOL) 5 mg annually was more effective than tenofovir disoproxil fumarate (TDF) switching at increasing bone mineral density (BMD) over 24 months in HIV-infected, osteopenic adults. To determine whether the effects of ZOL would persist without further infusions, we compared changes in left hip and spine BMD over 36 months in participants randomized to ZOL 5 mg at baseline and month 12 (and to continue TDF) or to switch TDF (without receiving ZOL). We also compared changes in the plasma bone turnover markers (BTMs) C-terminal telopeptide of type 1 collagen (CTX; bone resorption), and procollagen type 1 N propeptide (P1NP; bone formation) and determined whether CTX and P1NP changes at month 3 predicted BMD changes at month 36. Changes were compared in the per-protocol populations, which included 32 (74%) of 43 participants randomized to ZOL and 37 (88%) of 42 participants who switched TDF. Despite not receiving ZOL after month 12, mean hip and spine BMD change from baseline were stable and remained greater with ZOL at month 36 than with TDF switching (spine: 7.5% versus 2.7%, mean difference 4.7%, p < 0.001; hip: 5.5% versus 1.5%, mean difference 4.0%, p < 0.001). CTX and P1NP levels declined in both groups but significantly more with ZOL. Only percent changes in P1NP at month 3 correlated inversely with BMD changes at month 36 (spine: rho = -0.442, p < 0.001; hip: rho = -0.373, p = 0.002). Two infusions of ZOL (in the presence of ongoing TDF) yielded sustained BMD increases through month 36 that remained greater than with TDF switching. © 2019 American Society for Bone and Mineral Research.

The Effect of Low Dose Oral Vitamin D on Bone Mineral Density Changes in HIV Patients: 36 Months Follow Up.

A high incidence of vitamin-D deficiency and abnormal bone mineral density (BMD) is reported among Human Immunodeficiency Virus (HIV) infected patients. The study highlighted the effect of oral low dose vitamin-D replacement in patients with a known vitamin- D deficiency on the levels of vitamin-D [25 (OH)D], parathyroid hormone (PTH) and Bone Mineral Density (BMD) of hip and spine. Patients took a daily low dose of 800IU of vitamin-D. The following details were collected on all patients: demographics, CD-4 cell count, viral load, fracture risk factors, treatment history, corrected calcium, alkaline phosphatase (ALP), Parathyroid Hormone (PTH) (intact PTH), vitamin D 25(OH)D, inorganic phosphate and BMD of hip and spine at baseline, 12 and 36 months. Our Cohort consisted of 86 patients. Patient details included: mean age 42.8 (+/-7.7) years, 48 (55%) females 64, (74%) black African, CD-4 count 440.7 (+/-180.8) cells/dL, plasma VL 1.6 log (+/-2.3) copies/mL, duration of illness 80.9 (34.1) months, duration of exposure to antiretroviral 65.2 (+/-27.9) months. At baseline, no difference in BMD of hip or spine was observed, however, a higher PTH (0.001) in patients taking Tenofivir and a lower vitamin-D was noticed in patients taking Efavirenz. After 36 months, patients on vitamin D replacement (n=44) had a significant increase in vitamin- D level (15.4 +/-10.4 vs 104.1+/-29.1 p=0.0001), lower PTH (6.3 +/-3.4 vs 4.4 +/-1.4 p=0.0001) ALP (108.9+/-78.8 vs 90.6+/-45.8 p=0.05) but no change in corrected calcium (2.13 +/-0.1 vs 2.16 +/-0.34 p=0.5) and BMD of spine (1.039+/-0.226 vs.1.027+/-0.211, p=0.77), and BMD of hip (1.020 +/- 0.205 vs. 1.039, p=0.61). In a multivariate logistic regression analysis that included all significant variables, vitamin-D replacement independently was associated with increase in vitamin- D level (OR 2.08, CI 1.03, 4.12, p=0.005), decrease in PTH level (OR 0.53, CI 0.35, 0.82, p=0.04), but not with change in corrected calcium, alkaline phosphatase, BMD of hip or spine. After 36 months of follow up, the replacement of low dose once daily oral vitamin-D in the treatment experienced HIV infected patients with vitamin-D deficiency can increase vitamin- D level, reduce PTH level without any change in BMD of spine and hip.

Change in Bone Density and Reduction in Fracture Risk: A Meta-Regression of Published Trials

Meta-analyses conducted >15 years ago reported that improvements in bone mineral density (BMD) were associated with reduction in vertebral and nonvertebral fractures in osteoporosis trials. Numerous studies have been conducted since then, incorporating new therapies with different mechanisms of action and enrolling many more subjects. To extend these prior analyses, we conducted a meta-regression of 38 placebo-controlled trials of 19 therapeutic agents to determine the association between improvements in BMD and reductions in fracture risk. We used a linear model to examine the relationship between mean percent difference in BMD change between treatment and placebo groups and the logarithm of the relative risk. We found that greater improvements in BMD were strongly associated with greater reductions in vertebral and hip fractures but not nonvertebral fractures. For vertebral fracture, the r2 values for total hip, femoral neck, and lumbar spine BMD change were 0.56, 0.54, and 0.63, respectively (p ≤ 0.0002). For a 2% or 6% improvement in total hip BMD, we might expect a 28% or 66% reduction, respectively, in vertebral fracture risk. For hip fracture, the r2 values for total hip, femoral neck, and lumbar spine BMD change were 0.48 (p = 0.01), 0.42 (p = 0.02), and 0.22 (ns), respectively. For a 2% or 6% improvement in total hip BMD, we might expect a 16% or 40% reduction in hip fracture risk. In conclusion, our results extend prior observations that larger improvements in dual-energy X-ray absorptiometry (DXA)-based BMD are associated with greater reductions in fracture risk, particularly for vertebral and hip fractures. Although these results cannot be directly applied to predict the treatment benefit in an individual patient, they provide compelling evidence that improvements in BMD with osteoporosis therapies may be useful surrogate endpoints for fracture in trials of new therapeutic agents. © 2019 American Society for Bone and Mineral Research.

Treatment with once-weekly alendronate oral jelly compared with once-weekly alendronate oral tablet for Japanese patients with primary osteoporosis: An open-label, prospective, observational study.

Background and aimsClinical data regarding alendronate jelly are limited. We compared the efficacy and safety of once‐weekly alendronate oral jelly with once‐weekly alendronate tablet formulations in the context of primary osteoporosis.MethodsIn this 6‐month, open‐label, prospective, observational study, Japanese patients aged ≥60 years with primary osteoporosis were included from 14 primary care centres in Japan. The effects of once‐weekly alendronate oral jelly and tablet formulations on bone mineral density (BMD), bone turnover markers, and quality of life related to gastrointestinal symptoms were assessed at baseline and 6 months. Treatment was allocated by patient preference. This potentially confounding factor was adjusted for statistically.ResultsIn total, 170 patients were enrolled (jelly, n = 97; tablet, n = 73). Mean percent changes in radius, lumbar spine, femoral neck, and hip BMD were similar in both treatment groups at 6 months. Both formulations decreased tartrate‐resistant acid phosphatase 5b (TRACP‐5b) and procollagen 1 N‐terminal peptide (P1NP) between baseline and 6 months (by about 50% and 60%, respectively); no significant differences in mean changes were noted in these markers between groups. At 6 months, no significant differences were noted in visual analogue scale or EuroQOL five‐dimension questionnaire scores between groups. The jelly group had significantly lower scores than the tablet group in the Izumo scale domains of heartburn (−0.81, P = 0.0040), epigastralgia (−0.94, P = 0.0003), and epigastric fullness (−0.49, P = 0.044). During treatment, more patients discontinued for upper gastrointestinal symptoms in the tablet group (n = 4) than the jelly group (n = 1).ConclusionsOnce‐weekly alendronate oral jelly 35 mg may be a suitable alternative therapeutic agent for primary osteoporosis in Japan.