Change In Femoral Neck Bone Mineral Density Research Articles

Effects of Multicomponent Home-Based Intervention on Muscle Composition, Fitness, and Bone Density After Hip Fracture.

Mechanistic factors on the pathway to improving independent ambulatory ability among hip fracture patients by a multicomponent home-based physical therapy intervention that emphasized aerobic, strength, balance, and functional training are unknown. The aim of this study was to determine the effects of 2 different home-based physical therapy programs on muscle area and attenuation (reflects muscle density) of the lower extremities, bone mineral density (BMD), and aerobic capacity. Randomized controlled trial of home-based 16 weeks of strength, endurance, balance, and function exercises (PUSH, n = 19) compared to seated active range-of-motion exercises and transcutaneous electrical neurostimulation (PULSE, n = 18) in community-dwelling adults >60 years of age within 26 weeks of hip fracture. In PUSH and PULSE groups combined, the fractured leg had lower muscle area and muscle attenuation and higher subcutaneous fat than the nonfractured leg (p < .001) at baseline. At 16 weeks, mean muscle area of the fractured leg was higher in the PUSH than PULSE group (p = .04). Changes in muscle area were not significantly different when compared to the comparative PULSE group. There was a clinically relevant difference in change in femoral neck BMD between groups (p = .05) that showed an increase after PULSE and decrease after PUSH. There were generally no between-group differences in mean VO2peak tests at 16-week follow-up, except the PUSH group reached a higher max incline (p = .04). The treatment effects of a multicomponent home-based physical therapy intervention on muscle composition, BMD, and aerobic capacity were not significantly different than an active control intervention in older adults recovering from hip fracture. ClinicalTrials.gov Identifier: NCT01783704.

Coronary artery calcification is associated with smaller increases in femoral neck bone mineral density with anti-resorptive therapy

Abstract Introduction Patients with osteoporosis are at high cardiovascular risk, partly due to vascular calcification, such as in the coronary vessels. It is uncertain if the presence of coronary artery calcification (CAC) effects bone mineral density (BMD) response to anti-resorptive treatment – first line therapy for osteoporosis. We therefore assessed changes in BMD following initiation of anti-resorptive treatment for osteoporosis in patients with and without evidence of CAC. Methods Individuals dispensed at least one prescription for an anti-resorptive medication (bisphosphonates or denosumab) at Monash Health between 2009-2022 were identified. Unique record numbers for these individuals were then cross-matched against the cardiac CT imaging service at Monash Heart (HREC#73603). CAC was detected using a 320-slice CT coronary angiogram (CTCA). We included only those patients having a baseline BMD measurement within two years of CTCA. The annualised percentage change in femoral neck BMD was calculated and adjusted for age, sex, height, weight, and number of years on anti-resorptive treatment. Results 106 individuals were identified of which 85 (women=70 [85%], median age=73 years [interquartile range 64-79 years]) had a follow-up BMD measurement including 19 with, and 66 without, evidence of CAC. Those with CAC were older (76 years versus 64 years, p&amp;lt;0.001). There were 70 bisphosphonate users and 15 denosumab users. Individuals with evidence of CAC experienced, on average, a 1.2% lower increase [(0.345% (0.343 to 0.348) versus -0.881% (-0.883 to -0.879), mean difference -1.226% (-1.493 to -0.959; p&amp;lt;0.05)] in annualised femoral neck BMD with anti-resorptive therapy after adjusting for important clinical risk factors. Interpretation These preliminary data suggests that CTCA-determined CAC may negatively impact femoral neck BMD increases with anti-resorptive therapy. This is perhaps consistent with existing and evolving hypotheses of dysregulatory processes driving ectopic calcium deposition, which we surmise would partially counter the effects of anti-resorptive therapy and potentially manifest as CAC. Thus, of particular interest will be the comparison of cardiovascular outcomes of patients with known CAC with and without anti-resorptive therapy, with the hypothesis that anti-resorptive therapy may potentially have cardioprotective effects in context of CAC. Analysis of the full cohort is underway.Table 1

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

Precedence of Bone Loss Accompanied with Changes in Body Composition and Body Fat Distribution in Patients with Type 2 Diabetes Mellitus

A total of 596 patients with T2DM, including 308 male and 288 female patients, were included in the follow-up study; the median follow-up time was 2.17 years. We calculated the difference between the endpoint and the baseline of each body composition index and the annual rate. The research participants were divided into the increased body mass index (BMI) group, stable BMI group, and decreased BMI group. Some confounding factors were adjusted, such as BMI, fat mass index (FMI), muscle mass index (MMI), muscle/fat mass ratio (M/F), trunk fat mass index (TFMI), appendicular skeletal muscle mass index (ASMI), and appendicular skeletal muscle mass/trunk fat mass ratio (A/T). The linear analysis showed that ΔFMI and ΔTFMI were negatively correlated with the change in femoral neck BMD (ΔFNBMD) and ΔMMI, ΔASMI, ΔM/F, and ΔA/T were positively correlated with ΔFNBMD. The risk of FNBMD reduction in patients with increased BMI was 56.0% lower than that in patients with decreased BMI; also, the risk in patients with stable M/F was 57.7% lower than that in patients with decreased M/F. The risk in the A/T increase group was 62.9% lower than that in the A/T decrease group. A reasonable muscle/fat ratio is still beneficial to maintaining bone mass. Maintaining a certain BMI value is conducive to maintaining FNBMD. Simultaneously, increasing the proportion of muscle mass and reducing fat accumulation can also prevent FNBMD loss.

Impact of testosterone therapy on bone turnover markers in obese males with type 2 diabetes and functional hypogonadism

Methods Fifty-five obese males with type 2 diabetes mellitus and functional hypogonadism participated in a 2-year, double-blind, placebo-controlled study of testosterone undecanoate (TU). Bone turnover markers C-telopeptide of type I collagen (CTX) and procollagen I N-terminal propeptide (PINP) were assessed at baseline, 12 and 24 months. Bone mineral density (BMD) changes were evaluated after 24 months using dual-energy X-ray absorptiometry. Group T (n = 28) received TU both years. Group P (n = 27) received placebo first year and TU second year. Results CTX decreased in group P from 1055 (676–1344) to 453 (365–665) pmol/L (p < 0.001) and from 897 (679–1506) to 523 (364–835) pmol/L (p < 0.001) in T. PINP decreased by 4.30 ± 8.05 μg/L in group P (p = 0.030) and 4.64 ± 8.86 μg/L in T (p < 0.023) after first year of therapy. No femoral neck BMD changes were observed in 32 patients from both groups (n = 16 per group). Lumbar spine BMD increased (by 0.075 ± 0.114 g/cm2; p = 0.019) in group T following two years of treatment. Conclusions We observed decreased CTX, decreased PINP and increased lumbar spine BMD after two years of testosterone treatment. Clinical trials NCT03792321; retrospectively registered trial on 4 January 2019.

Assessment of the genetic and clinical determinants of hip fracture risk: Genome-wide association and Mendelian randomization study

SummaryHip fracture is the clinically most important fracture, but the genetic architecture of hip fracture is unclear. Here, we perform a large-scale hip fracture genome-wide association study meta-analysis and Mendelian randomization study using five cohorts from European biobanks. The results show that five genetic signals associate with hip fractures. Among these, one signal associates with falls, but not with bone mineral density (BMD), while four signals are in loci known to be involved in bone biology. Mendelian randomization analyses demonstrate a strong causal effect of decreased femoral neck BMD and moderate causal effects of Alzheimer’s disease and having ever smoked regularly on risk of hip fractures. The substantial causal effect of decreased femoral neck BMD on hip fractures in both young and old subjects and in both men and women supports the use of change in femoral neck BMD as a surrogate outcome for hip fractures in clinical trials.

Preoperative Thoracic Muscle Mass Predicts Bone Density Change After Parathyroidectomy in Primary Hyperparathyroidism.

Predicting bone mineral density (BMD) gain after parathyroidectomy may influence individualized therapeutic approaches for treating patients with primary hyperparathyroidism (PHPT). This study aimed to assess whether skeletal muscle mass data could predict BMD change after parathyroidectomy in patients with PHPT. This retrospective study collected data from 2012 to 2021 at Severance Hospital, Seoul, Korea. A total of 130 patients (mean age, 64.7 years; 81.5% women) with PHPT who underwent parathyroidectomy were analyzed. Thoracic muscle volume (T6-T7 level) was estimated using noncontrast parathyroid single photon emission computed tomography/computed tomography (SPECT/CT) scans and an automated deep-learning-based software. The primary outcome assessed was the change in femoral neck BMD (FNBMD, %) 1 year after parathyroidectomy. The median degree of FNBMD change after parathyroidectomy was + 2.7% (interquartile range: -0.9 to + 7.6%). Elevated preoperative PTH level was associated with lower thoracic muscle mass (adjusted β: -8.51 cm3 per one log-unit PTH increment, P = .045) after adjusting for age, sex, body mass index (BMI), and baseline FNBMD. One SD decrement in thoracic muscle mass was associated with lesser FNBMD (adjusted β: -2.35%, P = .034) gain and lumbar spine BMD gain (adjusted β: -2.51%, P = .044) post surgery after adjusting for covariates. Lower thoracic skeletal muscle mass was associated with elevated preoperative PTH levels in patients with PHPT. Lower skeletal muscle mass was associated with lesser BMD gain after parathyroidectomy, independent of age, sex, BMI, preoperative BMD, and PTH level.

Effects of exercise training on bone mineral density in adults living with HIV: a retrospective study

Background: Evidence on the effects of exercise training on the bone health of men and women living with HIV (MLHIV and WLHIV) is limited. Objective: To investigate the effects of a long-term multimodal exercise program on the bone mineral density (BMD) of MLHIV and WLHIV. Methods: A retrospective cohort of 39 patients (13 women; 48.4 ± 7.6 y; HIV-infection for 15.5 ± 6.5 y; combined antiretroviral therapy for 12.2 ± 7.0 y) performed a multimodal exercise program (60-min sessions of aerobic, resistance, and flexibility exercises performed 3 times/week for 9–106 months). MLHIV and WLHIV were allocated into groups showing either advanced osteopenia/osteoporosis or normal BMD (+ or −). Results: MLHIV+ increased BMD at the femoral neck, total femur, and lumbar spine (∼3–4%) compared to MLHIV− (p ≤ 0.03). Changes in whole-body BMD were similar between MLHIV groups (p = 0.55). WLHIV+ exhibited higher loss of BMD at the femoral neck (∼6%) than WLHIV− (p = 0.04), whereas reductions in the whole-body, total femur, and lumbar spine (∼3–5%) were similar between groups (p ≥ 0.25). Among men, changes in femoral neck BMD were inversely correlated to femoral neck T-score (r = −0.62; p < 0.001), but not to the time of follow-up, appendicular skeletal muscle mass (ASM) index, or age (p ≥ 0.08). In women, these changes were inversely correlated with time of follow-up (r = −0.58) and age (r = −0.70) and positively correlated with femoral neck T-score (r = 0.46) and ASM index (r = 0.47) (p < 0.01). Conclusion: Multimodal exercise training may improve the BMD in people living with HIV, especially men with advanced osteopenia/osteoporosis. Adjuvant therapies to exercise should be considered to counteract losses in WLHIV.

Integrating real-world data and modeling to project changes in femoral neck bone mineral density and fracture risk in premenopausal women.

Decline of bone mineral density (BMD) during menopause is related to increased risk of fractures in postmenopausal women, however, this relationship in premenopausal women has not been established. To quantify this relationship, real‐world data (RWD) from the National Health and Nutrition Examination Survey (NHANES), and longitudinal data from the elagolix phase III clinical trials were modeled across a wide age range, and covariates were evaluated. The natural changes in femoral neck BMD (FN‐BMD) were well‐described by a bi‐exponential relationship with first‐order BMD formation (k1) and resorption (k2) rate constants. Body mass index (BMI) and race (i.e., Black) were significant predictors indicating that patients with high BMI or Black race experience a relatively lower BMD loss. Simulations suggest that untreated premenopausal women with uterine fibroids (UFs) from elagolix phase III clinical trials (median age 43 years [minimum 25–maximum 53]) lose 0.6% FN‐BMD each year up to menopausal age. For clinical relevance, the epidemiological FRAX model was informed by the simulation results to predict the 10‐year risk of major osteoporotic fracture (MOF). Premenopausal women with UFs, who received placebo only in the elagolix phase III trials, have a projected FN‐BMD of 0.975 g/cm2 at menopause, associated with a 10‐year risk of MOF of 2.3%. Integration of modeling, RWD, and clinical trials data provides a quantitative framework for projecting long‐term postmenopausal risk of fractures, based on natural history of BMD changes in premenopausal women. This framework enables quantitative evaluation of the future risk of MOF for women receiving medical therapies (i.e., GnRH modulators) that adversely affect BMD.

Calcium, Phosphorus, and Niacin Intakes During Late Pregnancy Are Positively Associated with Maternal Bone Mineral Density: A Pilot Study

Abstract Objectives The adequate calcium intake during pregnancy on postpartum bone mineral density (BMD) and neonatal outcomes are unknown as results of recent intervention trials are inconsistent. We investigated the relationship between maternal nutrient intake and maternal BMD at delivery, newborn birth outcomes, and maternal bone loss during lactation in Korean mothers. Methods Thirty Korean pregnant women (mean age: 34 years) were enrolled before delivery. Maternal food and supplement intake and BMD were assessed twice: at delivery (T1) and at weaning or 6 months postpartum (T2). Third trimester and postpartum food intake was assessed by food frequency questionnaire at T1 and T2, respectively, and analyzed for intake of calcium and 22 major nutrients. Calcium intake was assessed as a continuous variable or categorized as &amp;lt; or ≥500 mg/d. Maternal lumbar spine (LS), femoral neck (FN), trochanter, and intertrochanter BMD were measured by dual energy X-ray absorptiometry. Birth length, birth weight, and head circumference of neonates were collected. Participants were categorized according to duration of lactation. General linear models were adjusted for covariates. Results Mean ± STD calcium intake was 905 ± 430 mg/d at T1 and 608 ± 227 at T2 (change: P = 0.05). Women with calcium intakes &amp;lt;500 mg/d had lower LS BMD at T1 (P = 0.026). No difference was detected at other study sites. Phosphorus and niacin intakes during the third trimester were positively correlated with T1 LS BMD (ß: 0.162 and 0.088, respectively; both P &amp;lt; 0.05). Birth weight and head circumference were negatively associated with T1 iron intake(ß: −9.065 and −0.0292, respectively; both P &amp;lt; 0.05). Intake of other nutrients during late pregnancy were not associated with maternal T1 BMD or neonatal outcomes. Among the 10 participants that completed the second visit, 6 women breastfed. Postpartum bone change was not associated with breastfeeding. Energy intake at T2 was negatively associated with change in FN BMD (ß: −0.007, P &amp;lt; 0.001). Postpartum intake of other nutrients was not associated with change of BMD at any site. Conclusions Intakes of calcium, phosphorus, and niacin during the third trimester are positively associated with maternal LS BMD, but not neonatal birth outcomes, in Koreans. Breastfeeding and postpartum calcium intake may not affect bone after birth. Funding Sources National Research Foundation of Korea.

The Impact of Different Modes of Exercise Training on Bone Mineral Density in Older Postmenopausal Women: A Systematic Review and Meta-analysis Research

Effectiveness of exercise on bone mass is closely related to the mode of exercise training regimen, as well as the study design. This study aimed to determine the effect of different modes of exercise training on lumbar spine and femoral neck bone mineral density (BMD) in older postmenopausal women (PMW). PubMed, CINAHL, Medline, Google Scholar, and Scopus databases and reference lists of included studies were searched up until March 25, 2019 for randomized controlled trials (RCTs) that evaluated the effectiveness of various modes of exercise training in PMW. Sixteen RCTs with 1624 subjects were included. Our study found no significant change in both lumbar spine and femoral neck BMD following exercise training (MD: 0.01g/cm2; 95% confidence interval (CI) [- 0.01, 0.02] and MD: 0.00g/cm2; 95% CI [- 0.01, 0.01], respectively). However, subgroup analysis by type of exercise training revealed that lumbar spine BMD (MD: 0.01; 95% CI [0.00, 0.02]) raised significantly when whole-body vibration (WBV) was employed as intervention compared with RCTs that utilized aerobic (MD: - 0.01; 95% CI [- 0.02, - 0.01]), resistance (MD: 0.01; 95% CI [- 0.04, 0.06]), and combined training (MD: 0.03; 95% CI [- 0.01, 0.08]). On the other hand, lumbar spine BMD (MD: - 0.01; 95% CI [- 0.02, - 0.01]) reduced significantly when aerobic exercise training was used as intervention compared with RCTs that utilized resistance training, combined training, and WBV. By contrast, these analyses did not have significant effect on change in femoral neck BMD. WBV is an effective method to improve lumbar spine BMD in older PMW.

The impact of switching once-weekly teriparatide to denosumab in osteoporosis patients

BackgroundIt has been reported that switching from daily (d) teriparatide (TPTD) to denosumab (DMAb) is effective for severe osteoporosis patients. However, there have been no reports about switching from weekly (w) TPTD to DMAb in patients with osteoporosis. Once-weekly 56.5-μg TPTD treatment increases bone mineral density (BMD) and reduces fracture events. The objective of the current retrospective study was to elucidate the impact of switching w-TPTD to DMAb in patients with osteoporosis. MethodsIn this study, 40 patients were treated with w-TPTD for 18 months and then switched to DMAb for 18 months. The sample included 2 men and 38 women with a mean age of 74.5 (60–85) years. Twenty-five subjects had primary osteoporosis, and 15 had secondary osteoporosis. The mean number of osteoporotic vertebral fractures was 4.1. Serum bone turnover markers and BMD were evaluated every 6 months. ResultsBone alkaline phosphatase (BAP) and tartrate resistant acid phosphatase 5b (TRACP5b), markers of bone formation and resorption respectively, were not significantly different in w-TPTD subjects at 18 months compared with those at baseline (p > 0.05), but BAP and TRACP5b in subjects treated with DMAb were significantly lower at 36 months compared with those at baseline (p < 0.05). BMD of the lumbar spine (LS), femoral neck (FN), and total hip (TH) increased by 12.3%, 2.5%, and 2.2% by 36 months with DMAb treatment, significantly higher than at baseline (p < 0.05). Changes in BMD of FN and TH in primary osteoporosis patients were significantly higher than in secondary osteoporosis patients at 18 months (w-TPTD) and 36 months (DMAb, p < 0.05). ConclusionBMD significantly increased in osteoporosis patients switched from w-TPTD to DMAb. However, the impact of switching from w-TPTD to DMAb in secondary osteoporosis patients was not as great as in primary osteoporosis patients at the view points of changes in BMD of FN and TH.

Bone Loss at the Hip and Subsequent Mortality in Older Men: The Osteoporotic Fractures in Men (MrOS) Study.

Low bone mineral density (BMD) is associated with increased mortality risk, yet the impact of BMD loss on mortality is relatively unknown. We hypothesized that greater BMD loss is associated with increased mortality risk in older men. Change in femoral neck BMD was assessed in 4400 Osteoporotic Fractures in Men (MrOS) study participants with two to three repeat dual‐energy X‐ray absorptiometry scans over an average of 4.6 ± 0.4 (mean ± SD) years. Change in femoral neck BMD was estimated using mixed effects models; men were grouped into three categories of BMD change: maintenance (n = 1087; change ≥ 0 g/cm2); expected loss (n = 2768; change between 0 g/cm2 and <1 SD below mean change [>–0.034 g/cm2]); and accelerated loss (n = 545; change 1 SD below mean change or worse [≤–0.034 g/cm2]). Multivariate proportional hazards models adjusted for potential confounders estimated the risk of all‐cause mortality over 8.1 ± 2.8 years following visit 2. Mortality was centrally adjudicated by physician review of death certificates. At visit 1, mean age was 72.9 ± 5.5 years. Men who maintained BMD were less likely to die during the subsequent follow‐up period (33.7%) than men who had accelerated BMD loss (60.6%) (p < 0.001). Compared to men who had maintained BMD, those who had accelerated BMD loss had a 44% greater risk of mortality in multivariate‐adjusted models (HR, 1.44; 95% CI, 1.23 to 1.68). Compared to men who had maintained BMD, there was no significant difference in mortality risk for men with expected loss of BMD (36.9% died) (multivariate HR, 1.00; 95% CI, 0.89 to 1.13). Further adjustment for visit 1 or visit 2 BMD measurement did not substantially alter these associations. Results for total hip BMD were similar. In conclusion, accelerated loss of BMD at the hip is a risk factor for mortality in men that is not explained by comorbidity burden, concurrent change in weight, or physical activity. © 2017 The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.

Effects of water-based exercise on bone health of middle-aged and older adults: a systematic review and meta-analysis.

BackgroundAge-related bone loss is a major health concern. Only exercises associated with high-impact and mechanical loading have been linked to a positive effect on bone turnover; however, these types of exercises may not always be appropriate for middle-aged and older adults due to physical decline or chronic disorders such as osteoarthritis. Water-based exercise (WBE) has been shown to affect different components of physical fitness, has lower risks of traumatic fracture, and applies less stress to joints. However, the effects of WBE on bone health are unclear.ObjectiveThis study aimed to explore whether WBE is effective in preventing age-related bone deterioration in middle-aged and older adults.MethodsA search of relevant databases and the references of identified studies was performed. Critical narrative synthesis and meta-analyses were conducted.ResultsEleven studies, involving 629 participants, met all inclusion criteria. All participants were postmenopausal women. Eight studies compared WBE to a sedentary control group, and four studies had land-based exercise (LBE) participants as a comparison group. Meta-analyses revealed significant differences between WBE and control group in favor of WBE for changes in bone mineral density (BMD) at the lumbar spine (mean difference [MD] 0.03 g/cm2; 95% confidence interval [CI]: 0.01 to 0.05) and femoral neck (MD 0.04 g/cm2; 95% CI: 0.02 to 0.07). Significant differences were also revealed between WBE and LBE in favor of LBE for changes in lumbar spine BMD (MD −0.04 g/cm2; 95% CI: −0.06 to −0.02). However, there was no significant difference between WBE and LBE for changes in femoral neck BMD (MD −0.03 g/cm2; 95% CI: −0.08 to 0.01).ConclusionWBE may have benefits with respect to maintaining or improving bone health in postmenopausal women but less benefit when compared to LBE. Further research is required on this topic.

Efficacy of Daily Teriparatide Treatment in Low Levels of Walking State Patients.

Little is known about the efficacy of osteoporosis medication in patients with low levels of walking state, namely, influence by immobilization levels. We retrospectively compared the efficacy of the daily teriparatide therapy in patients with low and high levels of walking state to detect possible immobilization-related differences. We analyzed 661 patients treated with 20μg/day of teriparatide for 24months. We measured the changes in the bone mineral density (BMD) of the lumbar spine (LS) and of the femoral neck (FN), the changes in serum procollagen type I N-terminal propeptide (PINP) levels and urinary N-telopeptide (uNTX) excretion. To compare the results of BMD and bone turnover marker, the patients were divided into two subgroups, low levels of walking state and high levels of walking state. Compared with baseline, in the low levels of walking state subgroup, the percent LS BMD and FN BMD increased significantly by 12.8±8.9% and 5.0±13.8% at 24months, respectively (p<0.01 vs baseline for LS and FN, respectively); the mean absolute LS BMD and FN BMD change was 0.101±0.067g/cm2 and 0.017±0.063g/cm2 at 24months, respectively. In the high levels of walking state subgroup, the percent LS BMD and FN BMD increased significantly by 13.4±9.5% and 3.1±7.8% at 24months, respectively; the mean absolute LS BMD and FN BMD change was 0.104±0.068g/cm2 and 0.017±0.042g/cm2 at 24months, respectively. The increases in percent and absolute BMD in LS and FN, and the changes in PINP and uNTX were similar between the subgroups. The efficacy of the daily teriparatide treatment is similar between low levels of walking state patients and high levels of walking state patients and was not influenced by immobilization levels.

53 - A Risk-Adapted Protocol of Prophylactic Zoledronic Acid Prevents Bone Mineral Density Loss Post Allograft: Results of the ALLG Bm07 Phase II Prospective Trial

Bone loss occurs frequently following alloSCT and likely contributes to increased fracture risk after alloSCT. We previously demonstrated that monthly pamidronate reduced bone loss post-alloSCT and small studies have suggested that zoledronic acid (ZA) does likewise. However, bisphosphonates are expensive and not all patients require frequent prophylaxis. The Australasian Leukemia & Lymphoma Group (ALLG) conducted a prospective study evaluating the efficacy of pre-transplant ZA and individualized post-transplant ZA to prevent bone loss in patients undergoing alloSCT. Methods: A phase II multicenter study was conducted in adult alloSCT recipients. All patients received ZA 4 mg prior to conditioning. Bone mineral density (BMD) was measured pre-alloSCT and at days 100, 180, 270 and 365 post-alloSCT. Administration of post-transplant ZA was determined by a risk-adapted algorithm. Following each assessment, patients with any of: i) reduction in BMD >5% compared with baseline, ii) who received ≥1 mg/kg/day prednisolone for 2 weeks, iii) ≥ 10 mg/d prednisolone for 6 weeks were given ZA. All patients received vitamin D and calcium supplementation. Pre-menopausal women received hormone replacement therapy. The primary endpoint was the change in femoral neck (FN) BMD at days 100 (d100) and 365 (d365) post-alloSCT compared with baseline. The secondary objective was a comparison of FN BMD with 35 historical untreated controls at d100 and d365. Results: Of 82 patients enrolled, 70 were alive without relapse at d100. By d100, 44 (62.9%) received glucocorticosteroids, including 35 (50%) with mean prednisolone dose >10 mg/d. At d100, FN BMD change was -2.6 ± 4.6% compared to baseline (P = n.s) (Figure 1). Factors significantly associated with BMD loss at d100 included acute GVHD (P = .040 ANOVA overall difference grades 0-4) and busulfan/cyclophosphamide (Bu/Cy) conditioning (vs Cy/TBI mean difference -4.1%, P = .023; vs other regimens -3.5%, P = .034). BMD did not significantly change between d100 and d365. Factors associated with change in BMD at d365 included extensive chronic GVHD (vs no chronic GVHD mean difference -6.9%, P = .008) and Bu/Cy conditioning (vs Cy/TBI -6.0%, P = .007). Age, sex, cyclosporin duration and mean glucocorticoid dose stratified into low (<10 mg/d), medium (10-50 mg/d) or high (>50 mg/d) groups were not associated with change in BMD at d100 or d365. Compared with historical controls receiving no ZA, BMD loss at d100 and d365 was significantly less in patients who received ZA (d100 -2.6% vs -6.0%, P = .001; d365 -2.9% vs -10.5%, P < .0001). There were no serious adverse events attributed to ZA. Conclusion: Prophylactic ZA pre-alloSCT minimizes loss of FN BMD by d100 post-alloSCT. A risk-adapted algorithm based on serial BMD assessments and glucocorticoid exposure between d100 to d365 post-alloSCT prevents further loss of 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.

Young patients and those with a low eGFR benefitted more from denosumab therapy in femoral neck bone mineral density.

This study investigated the effect of different severities of CKD on femoral neck bone mineral density (BMD) in patients treated with denosumab. This study was a retrospective case review of CKD patients treated with denosumab. Baseline age, sex, and body mass index (BMI) were recorded for all patients. All comorbidities such as diabetes, hypertension, liver, and estimated glomerular filtration rate (eGFR) serum collagen type 1 cross-linked C-telopeptide (CTX) were also recorded. All subjects underwent dual energy X-ray absorptiometry assay of the femoral neck to determine the BMD. Changes in femoral neck BMD between baseline and 1year after denosumab administration were recorded. A total 108 patients with CKD who had received denosumab therapy were enrolled. The mean age was 71.04±9.64years, and 96 patients (88.9%) were women. Baseline eGFR correlated negatively with changes in the BMD of femoral neck (Rho =40.6, P<0.01). The lower the eGFR, the more was the improvement in BMD in the femoral neck after denosumab therapy. When changes in femoral neck BMD were assessed as outcome measures using linear regression, young patients (P=0.001) and those with a low eGFR benefitted more from denosumab therapy (P=0.029). Denosumab therapy is effective in cases of low eGFR and young age. Aggressive medical attention is needed in these patients.

Clinical effectiveness of bisphosphonates for the prevention of fragility fractures: A systematic review and network meta-analysis

ObjectivesTo assess the relative efficacy of bisphosphonates (alendronate, risedronate, ibandronate and zoledronic acid) for the treatment of osteoporosis using network meta-analysis (NMA). MethodsA systematic review of the literature was conducted using PRISMA guidelines. A network meta-analysis was used to determine the relative efficacy of treatments on four fracture outcomes (vertebral, non-vertebral, hip and wrist) and percentage change in femoral neck bone mineral density (BMD). Treatment effects were modelled using an exchangeable treatment effects model. Heterogeneity in treatment effects was explored by considering potential treatment effect modifiers using meta-regression. Where appropriate, inconsistency between direct and indirect evidence was assessed using node-splitting. Results46 randomised controlled trials (RCTs) were identified. Twenty seven RCTs provided fracture data and 35 RCTs provided BMD data for analysis. Zoledronic acid was associated with the greatest treatment effect on vertebral fractures (HR 0.41, 95% CrI: 0.28, 0.56) and percentage change in BMD (3.21, 95%: CrI 2.52, 3.86) compared to placebo. The greatest treatment effect on non-vertebral and wrist fractures was given by risedronate (HR 0.72, 95%: CrI 0.53, 0.89 and HR 0.77, 95%: CrI 0.44, 1.24, respectively). For hip fractures the greatest treatment effect was given by alendronate (HR 0.78, 95% CrI: 0.44, 1.30). ConclusionsAll treatments examined were associated with beneficial effects on fractures and femoral neck BMD relative to placebo. For vertebral fractures and percentage change in femoral neck BMD the treatment effects were statistically significant for all treatments. Pairwise comparisons between treatments indicated that no active treatment was statistically significantly more effective than any other active treatment for fracture outcomes. There was some heterogeneity in treatment effects between studies suggesting differential treatment effects according to study characteristics; however, there was no evidence of differential treatment effects with respect to gender and age.

A retrospective analysis of nonresponse to daily teriparatide treatment.

Some patients with osteoporosis do not respond to teriparatide treatment. Prior bisphosphonate use, lower bone turnover marker (BTMs) concentrations, and lower early increases in BTMs were significantly associated with a blunted lumbar spine (LS) bone mineral density (BMD) response to daily treatment with teriparatide, although the impact was limited. Some osteoporosis patients do not respond to teriparatide treatment. To better understand the factors underlying treatment nonresponses, we compared nonresponders' and responders' characteristics. We retrospectively analyzed 354 male and female patients with osteoporosis who were administered teriparatide (20μg/day) for 24months. The patients were categorized as responders (≥3% lumber spine (LS) bone mineral density (BMD) increase) or nonresponders (<3% LS BMD increase), and the groups were compared. The univariate analyses determined that prior bisphosphonate use, a lower baseline procollagen type I N-terminal propeptide (PINP) concentration and a lower urinary N-telopeptide of type I collagen (uNTX) concentration at baseline were significantly associated with teriparatide nonresponses, but these factors were not significant following multivariate analysis. Diminished early increases in the bone turnover markers (BTMs) were also related to nonresponses after teriparatide treatment began. In the nonresponders, the mean (standard deviation (SD)) absolute LS and femoral neck (FN) BMD changes were -0.002g/cm(2) (0.032) and -0.010g/cm(2) (0.045), respectively. In the responders, the mean (SD) absolute LS and FN BMD changes were 0.118g/cm(2) (0.056) and 0.021g/cm(2) (0.046), respectively. The serum PINP and uNTX levels increased rapidly in both groups, but the responders showed higher early absolute serum PINP and uNTX increases. The factors associated with nonresponses were prior bisphosphonate use, lower baseline BTM levels, and lower early increases in the BTMs after starting teriparatide treatment, but the impact of these factors on achieving a ≥3% LS BMD increase at 24months was limited.