Change In Total Hip Bone Mineral Density Research Articles

SAT183 What Determines Bone Mineral Density Changes After Successful Parathyroidectomy In Primary Hyperparathyroidism?

Abstract Disclosure: J.E. Mosquera: None. X. Li: None. N. Maalouf: None. Background: Parathyroidectomy (PTX) is the only cure for primary hyperparathyroidism (PHPT). However, the impact of PTX on bone mineral density (BMD) is very variable. Methods: To assess the impact of demographic and clinical characteristics on BMD change post-PTX, we retrospectively reviewed charts of patients with biochemically proven PHPT and successful PTX between 2006 and 2022 at our institution and who had available pre- and post-PTX DXA scans. We extracted available demographic, clinical, and laboratory data including age, gender, race, body mass index, pre-PTX serum parathyroid hormone, calcium, phosphorus, alkaline phosphatase (Alkphos), 25-OH-vitamin D, and creatinine, 24-hour urine calcium, and use of bisphosphonates. The association between these parameters and BMD changes were assessed using univariate and multivariate models. Results: 121 patients (107 women) were included in this analysis. 35% were African American and 50% Hispanic. At PTX, mean (SD) age was 59 (12) years, BMI was 33 (7) kg/m2. 36% had osteopenia and 47% had osteoporosis on pre-PTX DXA. 6% of patients used BP before PTX and 3% used BP within one year of PTX. At year 1 post-PTX, median BMD (25th-75th percentile) change was +2.7% (-0.2% - +6.6%) at the lumbar spine (LS), +2.4% (-0.5% - +5.9%) at the femoral neck (FN), +2.8% (0.7% - +4.7%) at total hip (TH), and +0.1% (-3.6% - +3.0%) at the 1/3 radius. In univariate analyses, 1-year change in FN BMD was positively associated with highest pre-PTX serum calcium, PTH, and Alkphos, and negatively associated with age and serum creatinine. TH BMD change at 1 year was positively associated with highest pre-PTX PTH and Alkphos, and negatively associated with lowest T-score at baseline, age, and pre-PTX serum phosphorus, 25-OH-D and creatinine. LS BMD change at 1 year was positively associated with highest pre-PTX serum calcium and PTH, and negatively associated with lowest phosphorus pre-PTX. In multivariate analyses, younger age, highest pre-PTX serum calcium, and lowest BMD T-score pre-PTX were all independently and significantly associated with greater increase in post-PTX BMD at the FN, TH, and LS. Moreover, pre-PTX Alkphos was associated with greater BMD gain at the FN and TH, while female gender was associated with greater gain in LS BMD. Conclusions: In patients with PHPT who undergo curative PTX, variable BMD changes are observed at 1-year post-PTX. Younger age at PTX, higher serum calcium, and lower BMD pre-PTX are all associated with greater BMD gains post-PTX. These findings should be considered in the counseling of PHPT patients undergoing PTX. Presentation: Saturday, June 17, 2023

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.

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 trabecular bone score and bone mineral density changes in Chinese antiretroviral-treated HIV-infected individuals.

HIV infection and antiretroviral therapy (ART) have been associated with decreased bone mineral density (BMD). This study aims to evaluate long-term changes in trabecular bone score (TBS), a novel index that estimates bone microarchitecture, and BMD among Chinese persons with HIV (PWH) treated with ART. We conducted a retrospective chart review of adult PWH at a large tertiary care hospital in China. Patients who had a DXA scan prior to ART and at least one follow-up DXA after ART initiation were included. Subgroup analyses examined the TBS and BMD changes in patients who switch from a non-TDF-containing regimen to one containing TDF, as compared to those who did not switch. Four hundred fifty-nine PWH were included. Among 68 patients ≥ 50 years, 13 patients (19.1%) had a normal BMD but partially degraded or degraded TBS. The mean percent decrease in lumbar spine (LS) BMD nadired at 48 weeks after ART initiation and then gradually improved. Percent decrease in femoral neck (FN) and total hip (TH) BMD nadired at 96 weeks and remained stably low thereafter. After switch to a TDF-containing regimen, only percent change in TH BMD was significant (-3.2%, p = 0.006). In the regression analyses, switch to a TDF-containing regimen was not associated with long-term change in TBS or BMD. This is the first study among PWH to evaluate the long-term impact of ART on TBS and BMD. At baseline, approximately 20% of patients had a normal BMD but impaired bone microstructure based upon TBS. For patients with 5 years of exposure to ART, there is a stabilization of TBS and BMD after initial nadir in the first 144 weeks. However, FN BMD, TH BMD, and TBS remained low at 5 years relative to baseline.

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).

Bone mineral density, kidney function, weight gain and insulin resistance in women who switch from TDF/FTC/NNRTI to ABC/3TC/DTG.

Tenofovir disoproxil fumarate (TDF) is associated with reduced bone mineral density (BMD). We evaluated changes in BMD in women who switched from TDF, emtricitabine and a nonnucleoside reverse transcriptase inhibitor (TDF/FTC/NNRTI) to abacavir, lamivudine and dolutegravir (ABC/3TC/DTG). We conducted a randomized controlled trial in which women aged ≥40years were randomized 1:2 to continue TDF/FTC/NNRTI or switch to ABC/3TC/DTG. The primary endpoint was change in total hip BMD measured by dual-energy X-ray absorptiometry at week 48. Secondary endpoints were changes in BMD of the lumbar spine and femoral neck and markers of bone turnover and kidney function up to week 48. We conducted exploratory analyses of weight gain, insulin resistance and metabolic syndrome. Primary and secondary endpoints were analysed by linear regression, with multiple imputation for missing time points. In all, 91 women [mean age = 50.4 (standard deviation [SD] = 6.6) years, median CD4 cell count = 600 (interquartile range: 479-800) cells/µL] were randomized. Women who switched to ABC/3TC/DTG maintained viral suppression and experienced improvements in total hip BMD (mean adjusted difference = 1%, P=0.027) and lumbar spine BMD (3%, P=0.002), with no change in specific markers of bone turnover or renal tubular function. Although participants in the ABC/3TC/DTG arm gained more weight (1.8kg, P=0.046), the switch strategy was not associated with reduced insulin sensitivity or new-onset metabolic syndrome. Switching from TDF/FTC/NNRTI to ABC/3TC/DTG resulted in improved BMD. Although weight gain was common in women who switched from TDF/FTC/NNRTI to ABC/3TC/DTG, we did not detect adverse effects on glucose homeostasis. Larger studies need to confirm these findings.

Serial Bone Density Measurement and Incident Fracture Risk Discrimination in Postmenopausal Women

Repeated bone mineral density (BMD) testing to screen for osteoporosis requires resources. For patient counseling and optimal resource use, it is important for clinicians to know whether repeated BMD measurement (compared with baseline BMD measurement alone) improves the ability to discriminate between postmenopausal women who will and will not experience a fracture. To assess whether a second BMD measurement approximately 3 years after the initial assessment is associated with improved ability to estimate fracture risk beyond the baseline BMD measurement alone. The Women's Health Initiative is a prospective observational study. Participants in the present cohort study included 7419 women with a mean (SD) follow-up of 12.1 (3.4) years between 1993 and 2010 at 3 US clinical centers. Data analysis was conducted between May 2019 and December 2019. Incident major osteoporotic fracture (ie, hip, clinical spine, forearm, or shoulder fracture), hip fracture, baseline BMD, and absolute change in BMD were assessed. The area under the receiver operating characteristic curve (AU-ROC) for baseline BMD, absolute change in BMD, and the combination of baseline BMD and change in BMD were calculated to assess incident fracture risk discrimination during follow-up. Of 7419 participants, the mean (SD) age at baseline was 66.1 (7.2) years, the mean (SD) body mass index was 28.7 (6.0), and 1720 (23%) were nonwhite individuals. During the study follow-up (mean [SD] 9.0 [3.5] years after the second BMD measurement), 139 women (1.9%) experienced hip fractures, and 732 women (9.9%) experienced major osteoporotic fracture. In discriminating between women who experience hip fractures and those who do not, AU-ROC values were 0.71 (95% CI, 0.67-0.75) for baseline total hip BMD, 0.61 (95% CI, 0.56-0.65) for change in total hip BMD, and 0.73 (95% CI, 0.69-0.77) for the combination of baseline total hip BMD and change in total hip BMD. Femoral neck and lumbar spine BMD values had similar discrimination for hip fracture. For discrimination of major osteoporotic fracture, AU-ROC values were 0.61 (95% CI, 0.59-0.63) for baseline total hip BMD, 0.53 (95% CI, 0.51-0.55) for change in total hip BMD, and 0.61 (95% CI, 0.59-0.63) for the combination of baseline total hip BMD and change in total hip BMD. Femoral neck and lumbar spine BMD values had similar ability to discriminate between women who experienced major osteoporotic fracture and those who did not. Associations between change in bone density and fracture risk did not differ by subgroup, including diabetes, age, race/ethnicity, body mass index, or baseline BMD T score. The findings of this study suggest that a second BMD assessment approximately 3 years after the initial measurement was not associated with improved discrimination between women who did and did not experience subsequent hip fracture or major osteoporotic fracture beyond the baseline BMD value alone and should not routinely be performed.

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.

Community-based football in men with prostate cancer: 1-year follow-up on a pragmatic, multicentre randomised controlled trial.

BackgroundPhysical exercise has been shown to be effective in relation to fatigue, aerobic fitness, and lower body strength in men with prostate cancer. However, research into the clinically relevant effects of interventions conducted in heterogeneous patient populations and in real-life clinical practice settings is warranted.Methods and findingsWe conducted a pragmatic, multicentre, parallel randomised controlled trial in 5 Danish urological departments. Recruitment began in May 2015, the first participant was randomised in June 2015, and the last participant was included in February 2017. In total, 214 men with prostate cancer were randomly assigned to either 6 months of free-of-charge football training twice weekly at a local club (football group [FG]) (n = 109) or usual care (usual care group [UG]) (n = 105), including brief information on physical activity recommendations at randomisation. Participants were on average 68.4 (SD 6.2) years old, 157 (73%) were retired, 87 (41%) were on castration-based treatment, 19 (9%) had received chemotherapy, and 41 (19%) had skeletal metastases at baseline. In this 1-year follow-up study, we evaluated the effects of community-based football training on the following outcomes: primary outcome, quality of life; secondary outcomes: continuation of football after 6 months, hip and lumbar spine bone mineral density (BMD), mental health score, fat and lean body mass, and safety outcomes, i.e., fractures, falls, and hospital admissions. Intention to treat (ITT) and per protocol (PP) analyses were conducted. No statistically significant between-group difference was observed in change in prostate-cancer-specific quality of life (ITT: 1.9 points [95% CI −1.9 to 5.8], p = 0.325; PP: 3.6 points [95% CI −0.9 to 8.2], p = 0.119). A statistically significant between-group difference was observed in change in total hip BMD, in favour of FG (0.007 g/cm2 [95% CI 0.004 to 0.013], p = 0.037). No differences were observed in change in lumbar spine BMD or lean body mass. Among patients allocated to football, 59% chose to continue playing football after the end of the 6-month intervention period. At 1-year follow-up in the PP population, FG participants had more improvement on the Mental Component Summary (2.9 [95% CI 0.0 to 5.7], p = 0.048 points higher) than UG participants, as well as a greater loss of fat mass (−0.9 kg [95% CI −1.7 to −0.1], p = 0.029). There were no differences between groups in relation to fractures or falls. Hospital admissions were more frequent in UG compared to FG (33 versus 20; the odds ratio based on PP analysis was 0.34 for FG compared to UG). There were 3 deaths in FG and 4 in UG. Main limitations of the study were the physically active control group and assessment of physical activity by means of self-report.ConclusionsIn this trial, participants allocated to football appeared to have improved hip BMD and fewer hospital admissions. Men who played football more than once a week for 1 year lost fat mass and reported improved mental health. Community-based football proved to be acceptable, even when club membership was not subsidised.Trial registrationClinicalTrials.gov NCT02430792.

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.

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.

Bone mineral density and markers of bone turnover and inflammation in diabetes patients with or without a Charcot foot: An 8.5-year prospective case-control study

Background and aimsCharcot foot is a rare but severe complication to diabetes and peripheral neuropathy. It is still unclear if an acute Charcot foot has long-term effects on the bone metabolism. To investigate this, we conducted a follow-up study to examine if a previously acute Charcot foot has any long-term effects on bone mineral density (BMD) or local or systemic bone metabolism. MethodsAn 8.5-year follow-up case–control study of 44 individuals with diabetes mellitus, 24 of whom also had acute or chronic Charcot foot at the baseline visit in 2005–2007, who were followed up in 2015 with DXA scans and blood samples. Results21 of the 44 baseline participants participated in the follow-up. There were no difference in the change in total hip BMD from baseline to follow-up in either the Charcot or the control group (p = 0.402 and 0.517), and no increased risk of osteoporosis in the previous Charcot feet either. From baseline to follow-up, there was a significant difference in the change in levels of fsRANK-L in the Charcot group, but not in the control group (p = 0.002 and 0.232, respectively). At follow-up, there were no differences in fsRANK-L between the groups. The fsRANK-L/OPG ratio also significantly decreased from baseline to follow-up in the Charcot group (3.4 versus 0.5) (p = 0.009), but not in the control group (1.3 versus 1.1) (p = 0.302). ConclusionWe found that diabetes patients with an acute Charcot foot have an elevated fsRANK-L/OPG ratio, and that the level decreased from baseline to follow-up to be comparable to the level in diabetes patients without previous or current Charcot foot. We found no permanent effect of an acute Charcot foot on hip or foot BMD.

Two-year cortical and trabecular bone loss in CKD-5D: biochemical and clinical predictors.

This prospective 2-year study of chronic kidney disease on dialysis (CKD-5D) patients assessed trabecular and cortical bone loss at the hip and spine and examined potential demographic, clinical, and serum biochemical predictors of bone loss. Eighty-nine CKD-5D patients had baseline, year 1, and year 2 bone mineral density (BMD) measurements using dual X-ray absorptiometry (DXA) and quantitative computed tomography (QCT); concurrent blood samples were drawn and clinical variables recorded. No study treatments occurred. The 2-year total hip BMD change was -5.9% by QCT and -3.1% by DXA (p<0.001). Spinal BMD was unchanged. QCT total hip cortical mass and volume decreased (-7.3 and -10.0%); trabecular volume increased by 5.9% (ps<0.001). BMD changes did not vary with age, BMI, race, diabetes, smoking, or exercise. Patients with higher baseline BMD and shorter dialysis vintage lost more bone (p<0.05). Vitamin D analogs and phosphate binders were not protective against bone loss; cinacalcet was protective by univariate but not by multivariable analysis. CNS-affecting antihypertensives were protective against loss of BMD, cortical mass, cortical volume (ps<0.05) and trabecular mass (p=0.007). These effects remained after adjustment. BSAP correlated with changes in BMD, cortical mass, and volume (p<0.01) as did sclerostin (inversely). There was severe cortical bone loss at the hip best recognized by QCT. Patients with shorter dialysis vintage and less pre-existing bone loss lost more bone, while treatment with CNS-acting antihypertensives was protective. BSAP and sclerostin were useful markers of bone loss.

Impact of pioglitazone on bone mineral density and bone marrow fat content.

Use of the insulin sensitizer pioglitazone is associated with greater fracture incidence, although the underlying mechanisms are incompletely understood. This study aimed to assess the effect of pioglitazone treatment on femoral neck bone marrow (BM) fat content and on bone mineral density (BMD), and to establish if any correlation exists between the changes in these parameters. In this double-blind placebo-controlled clinical trial, 42 obese volunteers with metabolic syndrome were randomized to pioglitazone (45mg/day) or matching placebo for 1year. The following measurements were conducted at baseline and during the treatment: liver, pancreas, and femoral neck BM fat content (by magnetic resonance spectroscopy), BMD by DXA, abdominal subcutaneous and visceral fat, and beta-cell function and insulin sensitivity. Results were available for 37 subjects who completed the baseline and 1-year evaluations. At 12months, BM fat increased with pioglitazone (absolute change, +4.1%, p=0.03), whereas BM fat content in the placebo group decreased non-significantly (-3.1%, p=0.08) (p=0.007 for the pioglitazone-placebo response difference). Total hip BMD declined in the pioglitazone group (-1.4%) and increased by 0.8% in the placebo group (p=0.03 between groups). The change in total hip BMD was inversely and significantly correlated with the change in BM fat content (Spearman rho = -0.56, p=0.01) in the pioglitazone group, but not within the placebo group (rho = -0.29, p=0.24). Changes in BM fat with pioglitazone were predominantly observed in female vs. male subjects. Pioglitazone use for 12months compared with placebo is associated with significant increase in BM fat content at the femoral neck, accompanied by a small but significant decrease in total hip BMD.

Change in Trabecular Bone Score (TBS) With Antiresorptive Therapy Does Not Predict Fracture in Women: The Manitoba BMD Cohort.

Bone mineral density (BMD) and trabecular bone score (TBS), along with additional clinical risk factors, can be used to identify individuals at high fracture risk. Whether change in TBS in untreated or treated women independently affects fracture risk is unclear. Using the Manitoba (Canada) DXA Registry containing all BMD results for the population we identified 9044 women age ≥40 years with two consecutive DXA scans and who were not receiving osteoporosis treatment at baseline (baseline mean age 62 ± 10 years). We examined BMD and TBS change, osteoporosis treatment, and incident major osteoporotic fractures (MOFs) for each individual. Over a mean of 7.7 years follow-up, 770 women developed an incident MOF. During the interval between the two DXA scans (mean, 4.1 years), 5083 women initiated osteoporosis treatment (bisphosphonate use 80%) whereas 3961 women did not receive any osteoporosis treatment. Larger gains in both BMD and TBS were seen in women with greater adherence to osteoporosis medication (p for trend <0.001), and the magnitude of the increase was consistently greater for BMD than for TBS. Among treated women there was greater antifracture effect for each SD increase in total hip BMD change (fracture decrease 20%; 95% CI, 13% to 26%; p < 0.001), femoral neck BMD change (19%; 95% CI, 12% to 26%; p < 0.001), and lumbar spine BMD change (9%; 95% CI, 0% to 17%; p = 0.049). In contrast, change in TBS did not predict fractures in women who initiated osteoporosis treatment (p = 0.10). Among untreated women neither change in BMD or TBS predicted fractures. We conclude that, unlike antiresorptive treatment-related changes in BMD, change in lumbar spine TBS is not a useful indicator of fracture risk irrespective of osteoporosis treatment. © 2016 American Society for Bone and Mineral Research.

Sex Differences in the Effects of Weight Loss Diets on Bone Mineral Density and Body Composition: POUNDS LOST Trial.

Weight loss is associated with reduction in bone mineral density (BMD). The objective was to address the role of changes in fat mass (FM) and lean mass (LM) in BMD decline in both sexes. A 2-year randomized controlled trial, the Preventing Overweight Using Novel Dietary Strategies (POUNDS-LOST). The setting was the general community. Enrolled were 424 overweight and obese participants (mean age, 52 ± 9 y; 57% females). Intervention included weight loss diets differing in fat, protein, and carbohydrates. Main outcome measures were change in spine, total hip (TH), and femoral neck (FN) BMD and sex differences after dietary intervention. At baseline, a stronger correlation between BMD and body composition measurements was observed in women, primarily with LM (r = 0.419, 0.507, and 0.523 for spine, FN, and TH, respectively; all P < .001). In men, only LM correlated with hip BMD (r = 0.298; P < .001). Mean weight loss at 2 years was -6.9%, without differences among diets. Two-year changes in BMD were 0.005 (P = .04), -0.014 (P < .001), and -0.014 g/cm(2) (P < .001), at the spine, TH, and FN, respectively. These changes directly correlated with changes in LM in women (r = 0.200, 0.324, and 0.260 for spine, FN, and TH, respectively), whereas FM loss correlated only with changes in TH BMD (0.274; P < .001). In men, changes in LM (-0.323; P < .001) and FM (-0.213; P = .027) negatively correlated with changes in spine BMD. Weight loss diets result in sex-specific effects on BMD. Although men exhibited a paradoxical increase in spine BMD, women tended to decrease in BMD at all sites.

Effects of randomized rosuvastatin compared with placebo on bone and body composition among HIV-infected adults.

Statins have a beneficial effect on bone mineral density (BMD) and lean mass in some studies of HIV-uninfected adults; however, this has never been investigated in the setting of HIV infection. HIV-infected individuals on stable antiretroviral therapy with a low-density lipoprotein cholesterol level of 130 mg/dl or less and evidence of heightened immune activation or inflammation were randomized to rosuvastatin 10 mg daily or placebo for 96 weeks. This was a prespecified interim analysis at 48 weeks. Between-group and within-group differences were compared; multivariable regression models were constructed. Seventy-two individuals were randomized to statin therapy and 75 to placebo. Modest 48-week relative increases in trochanter BMD [0.9%; 95% confidence interval (95% CI) -0.9 to 0.6] and total hip BMD (0.6%; 95% CI 0.0-1.1) in the statin arm were significantly greater than placebo (P < 0.05). The relationship between statin use and total hip BMD change was robust to adjustment of age, sex, race and smoking status (P = 0.02) and strengthened by inclusion of baseline (P = 0.01) and week 48 change in soluble tumour necrosis factor-α receptor (sTNFR)-1 (P = 0.009). Relative increases in total body, trunk and limb fat were similar between statin and placebo arms (P ≥ 0.58). Although a significant gain in leg lean mass was seen in the statin arm, this was not significantly different compared with placebo (P = 0.36). The improvements seen in total hip BMD after 48 weeks of rosuvastatin therapy support further potential benefits of statin therapy in HIV, beyond a reduction of cardiovascular risk.

The effect of 6 versus 9 years of zoledronic acid treatment in osteoporosis: a randomized second extension to the HORIZON-Pivotal Fracture Trial (PFT).

While bisphosphonates reduce fracture risk over 3 to 5 years, the optimal duration of treatment is uncertain. In a randomized extension study (E1) of the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly-Pivotal Fracture Trial (HORIZON-PFT), zoledronic acid (ZOL) 5 mg annually for 6 years showed maintenance of bone mineral density (BMD), decrease in morphometric vertebral fractures, and a modest reduction in bone turnover markers (BTMs) compared with discontinuation after 3 years. To investigate the longer-term efficacy and safety of ZOL, a second extension (E2) was conducted to 9 years in which women on ZOL for 6 years in E1 were randomized to either ZOL (Z9) or placebo (Z6P3) for 3 additional years. In this multicenter, randomized, double-blind study, 190 women were randomized to Z9 (n = 95) and Z6P3 (n = 95). The primary endpoint was change in total hip BMD at year 9 vs. year 6 in Z9 compared with Z6P3. Other secondary endpoints included fractures, BTMs, and safety. From year 6 to 9, the mean change in total hip BMD was -0.54% in Z9 vs. -1.31% in Z6P3 (difference 0.78%; 95% confidence interval [CI]: -0.37%, 1.93%; p = 0.183). BTMs showed small, non-significant increases in those who discontinued after 6 years compared with those who continued for 9 years. The number of fractures was low and did not significantly differ by treatment. While generally safe, there was a small increase in cardiac arrhythmias (combined serious and non-serious) in the Z9 group but no significant imbalance in other safety parameters. The results suggest almost all patients who have received six annual ZOL infusions can stop medication for up to 3 years with apparent maintenance of benefits.

Relationship between pretreatment rate of bone loss and bone density response to once-yearly ZOL: HORIZON-PFT extension study.

Several studies have shown that high bone turnover is associated with greater rates of bone loss and greater bone mineral density (BMD) response to antiresorptive therapy in postmenopausal osteoporosis. However, it is not known whether greater rates of bone loss before therapy are associated with greater BMD response to antiresorptive therapy. In the HORIZON-PFT study and its extension, one group of women who were randomized to receive placebo for 3 years (years 1, 2, and 3) were then switched to zoledronic acid (ZOL) 5 mg annually for up to three injections (years 4, 5, and 6, P3Z3 arm) (n = 1223). We measured total hip BMD at baseline, 1, 2, and 3 years on placebo and at 4.5 and 6 years on ZOL. The procollagen type I N-terminal propeptide (PINP) was measured at 3, 4.5, and 6 years. By design, not all subjects were followed for as long as 6 years, so this analysis focused on the results at 4.5 years. Those with the largest loss in total hip BMD on placebo in years 0 to 3 had the largest gain during ZOL (years 3 to 4.5): (r = -0.39, p < 0.0001). The change in total hip BMD in years 0 to 3 on placebo was related to the serum PINP at the end of the 3-year period (r = -0.24, p < 0.0001). The change in total hip BMD on ZOL from year 3 to 4.5 was related to the serum PINP at the end of the 3-year period (r = 0.26, p < 0.0001). We conclude that BMD response to ZOL is greater in postmenopausal women who had larger loss before treatment. This association may result from higher bone turnover being associated with both greater bone loss on placebo and greater BMD response to ZOL.