Change In Lumbar Spine Bone Mineral Density Research Articles

Influence of Prevalent Vertebral Fracture on the Correlation between Change in Lumbar Spine Bone Mineral Density and Risk of New Vertebral Fracture: A Meta-Analysis of Randomized Clinical Trials.

The correlation between change in bone mineral density (BMD) and the incidence of new vertebral fracture has been drawing attention in regard to evaluation of fracture risk and drug efficacy. We investigated the impact of the prevalence of vertebral fracture on this correlation via a meta-regression analysis with a view to improving evaluation of the correlation. A total of 19 postmenopausal osteoporosis clinical studies involving 62,432 patients in 46 placebo or treatment groups were identified through MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials. We performed a multivariate meta-regression analysis to examine the correlation between the percentage change in lumbar spine BMD from baseline at 3years and the proportion of subjects experiencing new vertebral fractures, with or without the proportion of subjects with prevalent vertebral fracture as a covariate. We also analyzed the interaction between the subgroups divided by the proportion of subjects with prevalent vertebral fracture and the percentage change in lumbar spine BMD from baseline at 3years. A multivariate meta-regression analysis showed a significant correlation between the change in lumbar spine BMD and the proportion of subjects experiencing new vertebral fracture, and a lower Akaike information criterion was obtained when the proportion of subjects with prevalent vertebral fracture was added as an explanatory variable. Significant interaction between the proportion of subjects with prevalent vertebral fracture and the change in lumbar spine BMD was shown. The change in lumbar spine BMD, not BMD T-score at one timepoint, had a significant correlation with the incidence of vertebral fracture. The prediction of the fracture risk by change in lumbar spine BMD was improved by adjusting the proportion of subjects with prevalent vertebral fracture in the study population. The difference of prevalence of vertebral fracture among populations should be considered when the association between change in lumbar spine BMD and incidence of vertebral fracture is examined.

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.

Effectiveness of anti-osteoporotic treatment after successful parathyroidectomy for primary hyperparathyroidism: a randomized, double-blind, placebo-controlled trial

PurposeAfter successful surgery for primary hyperparathyroidism, bone mineral density (BMD) does not improve equally in all patients. As no trial has so far aimed to influence normalization of BMD, it was the goal of this investigation to determine whether pharmacological treatment is effective in improving regain of BMD after successful parathyroidectomy in patients with preoperatively diagnosed osteoporosis or osteopenia and to evaluate when treatment may be indicated.MethodsIn this randomized, placebo-controlled, double-blind trial, 52 patients were treated with strontium ranelate 2 g daily + 1000 mg calcium + 800 IU vitamin D (strontium group; SG) or with 1000 mg calcium + 800 IU vitamin D alone (placebo group; PG) for 1 year. The main outcome measures were BMD (lumbar spine, femoral neck, radius) and bone turnover markers.ResultsThe baseline characteristics were similar in both groups. Absolute BMD (1.007 ± 0.197 vs. 0.897 ± 0.137 g/cm2; p = 0.024) and both relative (9.94 vs. 3.94%; p < 0.001) and absolute (0.09 ± 0.06 vs. 0.03 ± 0.04 g/cm2; p < 0.001) changes in lumbar-spine BMD were significantly higher in the SG than in the PG. Compared to baseline, BMD significantly increased in both groups at the lumbar spine (p < 0.001 and p = 0.001, respectively) and femoral neck (both p < 0.001), whereas radius BMD only changed significantly in the SG. However, the proportion of patients with osteoporosis/osteopenia significantly declined only at the lumbar spine in the SG (from 69.0 to 37.9%; p = 0.034), whereas no decrease was found in the PG. No severe adverse events occurred.ConclusionsPostoperative anti-osteoporotic treatment can positively influence regain of BMD mainly in the lumbar spine and should be considered. Without treatment, most patients and especially those with low preoperative markers of bone turnover remained osteoporotic/osteopenic 1 year after surgery.

Study of twice-weekly injections of Teriparatide by comparing efficacy with once-weekly injections in osteoporosis patients: the TWICE study

SummaryA 48-week, multicenter, randomized, double-blind, double-dummy, active-controlled, non-inferiority trial (the TWICE study) conducted in Japanese primary osteoporosis patients with a high risk of fractures demonstrated that a 28.2-μg twice-weekly regimen of teriparatide can provide comparable efficacy to a 56.5-μg once-weekly regimen of teriparatide, while also improving safety.IntroductionWhile a 56.5-μg once-weekly regimen of teriparatide has high efficacy for osteoporosis, treatment continuation rates are low, with one of the major causes being adverse drug reactions such as nausea or vomiting. The TWICE study was therefore conducted to investigate whether a twice-weekly regimen with 28.2-μg teriparatide can provide comparable efficacy to the 56.5-μg once-weekly regimen while improving safety.MethodsA 48-week, multicenter, randomized, double-blind, double-dummy, active-controlled, non-inferiority trial was conducted in Japan. Patients with primary osteoporosis aged ≥ 65 years at high risk of fractures (n = 553) were randomly allocated to the 28.2-μg twice-weekly group (n = 277) or the 56.5-μg once-weekly group (n = 276). The primary endpoint was the percentage change in lumbar spine (L2–L4) bone mineral density (BMD) at final follow-up.ResultsThe percentage changes in lumbar spine (L2–L4) BMD at final follow-up in the 28.2-μg twice-weekly and 56.5-μg once-weekly groups were 7.3% and 5.9%, respectively; the difference (95% confidence interval [CI]) in percentage change was 1.3% (0.400–2.283%). Since the lower limit of the 95% CI was above the pre-specified non-inferiority margin (− 1.6%), non-inferiority of the 28.2-μg twice-weekly group was demonstrated. Adverse drug reactions were significantly less frequent in the 28.2-μg twice-weekly group (39.7% vs 56.2%; p < 0.01); the incidence of major adverse drug reactions was lower, and the number of subjects who discontinued due to adverse drug reactions was less in the 28.2-μg twice-weekly group.ConclusionsA 28.2-μg twice-weekly regimen of teriparatide can provide comparable efficacy to a 56.5-μg once-weekly regimen while improving safety.Clinical trial registrationJapicCTI-163477.

Effects of Exercise Intervention Program on Bone Mineral Accretion in Children and Adolescents with Cystic Fibrosis: A Randomized Controlled Trial.

To evaluate effect of one year exercise intervention program on bone mineral accrual in children and adolescent with cystic fibrosis (CF). Fifty-two CF children (mean age 149.79 mo) were randomized into experimental (15 boys and 10 girls) and control groups (15 boys and 12 girls). Experimental group performed prescribed exercises three times/week, while control group continued with routine physical activities for one year. Following were assessed at baseline and at one year: Bone mineral density (BMD) of whole body and lumbar spine, pulmonary function, exercise capacity, quality of life and habitual activity. Change in whole body and lumbar spine BMD over 12 mo in experimental group was lower by 0.006g/cm2 (95% CI -0.02 to 0.02) and higher by 0.001g/cm2 (95% CI -0.04 to 0.03) than controls, respectively. However, difference between groups was non-significant for both parameters. Experimental group had a significant improvement in their exercise capacity (p = 0.006), quality of life, and serum vitamin D (p = 0.007) levels. Differences between groups for changes in pulmonary function and habitual activity were non-significant. Exercise regime was not associated withsignificant improvement in BMD of CF patients, but it had a positive impact on both physical and psychological health of these patients.

Changes in bone mineral density and bone metabolism after sleeve gastrectomy: a systematic review and meta-analysis

BackgroundRoux-en-Y gastric bypass surgery adversely affects bone health. The evidence is less well-described for sleeve gastrectomy (SG). ObjectivesTo better characterize bone metabolism changes after SG. SettingSystematic review and meta-analysis. MethodsMEDLINE and EMBASE were searched through March 2019 for eligible studies assessing adults with obesity aged 18 years or older that underwent SG. Bone mineral density (BMD), serum calcium, serum phosphate, serum 25-hydroxyvitamin D, serum parathyroid hormone, or serum alkaline phosphatase were reported at baseline and after SG; and a follow-up duration was at least 6 months. Preoperative and postoperative mean of each outcome of interest and corresponding standard deviations were extracted from each study and the mean difference (MD) was calculated. Pooled MD was then calculated by combining MDs of each study using random-effects model. ResultsA total of 22 studies with 1905 patients with obesity that underwent SG were included. There were significant decreases in total hip BMD (pooled MD of −.06 g/cm2; 95% confidence interval −.09 to −.03; I2 = 0%) and femoral neck BMD (pooled MD of −.05 g/cm2; 95% confidence interval −.09 to −.02; I2 = 0%) after SG. No significant change in lumbar spine BMD was observed. There were significant increases in serum calcium, serum 25-hydroxyvitamin D, and serum phosphate. Serum parathyroid hormone was significantly decreased. Serum alkaline phosphatase was not significantly altered after SG. ConclusionsThe present study found a decreased BMD among patients with obesity after SG.

Effects of the anti-RANKL antibody denosumab on joint structural damage in patients with rheumatoid arthritis treated with conventional synthetic disease-modifying antirheumatic drugs (DESIRABLE study): a randomised, double-blind, placebo-controlled phase 3 trial

ObjectiveTo evaluate the efficacy of denosumab in suppressing joint destruction when added to conventional synthetic disease-modifying antirheumatic drug (csDMARD) therapy in patients with rheumatoid arthritis (RA).MethodsThis was a multi-centre, randomised,...

Effects of teriparatide in Chinese and Caucasian women with osteoporosis: bridging study on efficacy.

ObjectiveTo bridge the efficacy and compare the safety of the 24-week teriparatide treatment in a Chinese osteoporosis study (NCT00414973) to a large international trial (FPT, NCT00670501) to determine whether long-term results from the international study were applicable to Chinese patients.MethodsIn this post-hoc analysis, a propensity score matching method was used to select patients with similar baseline characteristics. Patients were female with osteoporosis at high risk of fracture, aged ≥55 years, and had no history of rheumatoid arthritis or corticosteroid use. Outcomes included percentage changes in lumbar-spine bone mineral density (LS-BMD) from baseline to 24 weeks, safety in matched-pair patients, and long-term percentage changes in LS-BMD and fragility fracture incidence in the matched fracture prevention trial (FPT) population. The determination of the acceptability of bridging results was based on the International Conference on Harmonization E5 guidelines.ResultsA total number of 228 patients from each study were matched and paired. Patients were similar at baseline (P-values >0.33) except for ethnicity (98% Caucasian for FPT). For changes in LS-BMD from baseline to week 24, treatment with teriparatide showed significantly greater increases (P-values <0.001; least-squares mean difference: 5.0% in the Chinese study and 5.4% in FPT) than comparator (calcitonin/placebo). The safety profiles over 24 weeks were similar between two studies. For matched-pair FPT patients, long-term changes in LS-BMD were significantly greater (least-squares mean difference: 11.5%, P<0.001) and the fragility fracture rate was marginally lower in the teriparatide group compared with the placebo group (13.1% vs 22.3%, P=0.070).ConclusionAssuming similar pharmacokinetic profiles for teriparatide between populations, comparable increases in LS-BMD and consistent safety profiles within 24 weeks of the treatment suggest long-term LS-BMD results from the FPT may be applicable to Chinese population.

SUN-LB075 Effects of Pegvisomant and Pasireotide LAR on Incidence of Vertebral Fractures in Patients with Acromegaly Resistant to Treatment with First-Line Somatostatin Analogs

Purpose: Osteopathy is an emerging complication of acromegaly characterized by increased bone turnover, deterioration in bone microarchitecture and high risk of vertebral fractures (VFs). In somatostatin analog (SSA)- resistant patients (pts), Pegvisomant (PegV) and Pasireotide LAR (Pasi) are used for acromegaly treatment, but their effect on skeletal health is still not defined. Methods: In a longitudinal international multicenter study, we evaluated incidence of radiological VFs in 55 pts (29F/26M), mean age 44.1 yrs (SD: 17) with acromegaly resistant to first line SSA. Results: At the study entry, prevalent VFs (lumbar, thoracic) were identified in 23 pts (41.8%): 42 mild and 3 moderate (Genant score) VF. Mean spine Z-score was -0.4 (-0.6 in PegV, -0.2 in Pasi group, respectively; p=0.49). Biochemical acromegaly control was reached in 22 / 31 pts on Peg-V (71%) and in 16/24 pts on Pasi (66.7%). During the follow-up (mean 89.9 months for PegV group and 50.5 months for Pasi group), incident VFs were detected in 16 pts (29.1%). Occurrence of incident VFs was associated with the presence of pre-existing VFs (p=0.009), persistence of active acromegaly (p=0.009) and with higher median value of serum IGF-I during follow-up (p=0.04). There were no significant differences in age, gender, initial treatment choice and changes in lumbar spine BMD. Incident VFs occurred in 7/9 pts not contolled on Peg-V and 2/8 pts not controlled on Pasi. Among pts with active disease at last visit, incident VFs occurred less frequently in pts on treatment with Pasi (25%) compared to Peg-V (77.8%), p=0.03, independently of the IGF-I values (p=0.9). In pts who reached acromegaly biochemical control, 5/17 (22.7%) on Peg-V and 2/14 (12.5%) pts on Pasi had incident VFs, p=0.4. In pts on Peg-V, factors associated with incident VFs during follow-up were persistence of active acromegaly and higher values of IGF-I (median IGF x ULN: 0.5 IQR:1.8 vs 2.6 IQR: 2.2 p=0.02). In pts treated with Pasi, we did not find any factors associated with incident VFs. Furthermore, in pts with biochemically controlled acromegaly, no factor was associated with incident VFs which occurred less frequently in pts treated with Pasi. Conclusion: Our data confirm that active acromegaly is the main determinant of VFs and show for the first time that pts with biochemically active disease treated with Pasi had lower risk of incident VFs vs those treated with Peg-V. Conversely, no significant drug-related differences in incident VFs in pts with controlled acromegaly were observed. Additional studies on larger populations and with longer follow-up are needed to confirm our data and disclose the mechanisms underlying our findings. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

The Effect of an Exercise Intervention During Early Lactation on Bone Mineral Density During the First Year Postpartum.

During lactation, women may lose up to 10% of bone mineral density (BMD) at trabecular-rich sites. Previous studies show that resistance exercise may slow BMD; however, the long-term effects of exercise on BMD during lactation have not been reported. To evaluate the effect of two 16-week exercise interventions (4- to 20-wk postpartum) in lactating women at 1-year postpartum on lumbar spine, total body, and hip BMD. To increase sample size at 1-year postpartum, two 16-week exercise interventions were combined for analysis. At 4-week postpartum, 55 women were randomized to intervention group (weight bearing aerobic exercise and resistance exercise) or control group (no exercise) for 16-week, with a 1-year postpartum follow-up. BMD was measured by dual-energy X-ray absorptiometry. Repeated-measures analysis of covariance was used to test for time and group differences for BMD controlling for prolactin concentration and dietary calcium at 1-year postpartum. Change in lumbar spine BMD was significantly different over time and between groups from 4-week to 1-year postpartum, when controlling for prolactin concentration and dietary calcium. There were no significant differences between groups in total body and hip BMD. These results suggest that resistance exercise may slow bone loss during lactation, resulting in higher BMD levels at 1-year postpartum.

Effects of Denosumab and Alendronate on Bone Health and Vascular Function in Hemodialysis Patients: A Randomized, Controlled Trial.

Mineral and bone disorders including osteoporosis are common in dialysis patients and contribute to increased morbimortality. However, whether denosumab and alendronate are effective and safe treatments in hemodialysis patients is not known. Thus, we conducted a prospective, three-center study of 48 hemodialysis patients who were diagnosed as having osteoporosis and had not received anti-osteoporotic agents previously. Participants were randomized to either denosumab or intravenous alendronate, and all subjects received elemental calcium and calcitriol during the initial 2 weeks. The primary endpoint was the percent change in lumbar spine bone mineral density (LSBMD) at 12 months of treatment. The secondary endpoints included the following: change in BMD at other sites; change of serum bone turnover markers (BTM), coronary artery calcium score (CACS), ankle-brachial pressure index (ABI), brachial-ankle pulse wave velocity (baPWV), flow mediated dilation (FMD), and intima-media thickness at the carotid artery (CA-IMT); change from day 0 to day 14 in serum levels of Ca and P; time course of serum calcium (Ca), phosphorus (P), and intact parathyroid hormone (i-PTH); new fractures; and adverse events. Initial supplementation with elemental calcium and calcitriol markedly ameliorated the decrease of serum corrected calcium (cCa) levels induced by denosumab during the first 2 weeks, whereas serum cCa levels in the alendronate group were increased. Denosumab and alendronate markedly decreased serum levels of BTM and increased LSBMD at 12 months compared with baseline. However, no significant differences were found in the changes in LSBMD between the two groups. The serum cCa, P, and i-PTH levels in the two groups were maintained within the appropriate range. In contrast to the anti-osteoporotic effects, no significant differences after 12 months of treatment were found in the CACS, CA-IMT, ABI, baPWV, and FMD compared with pretreatment in both groups. Denosumab and alendronate treatment improved LSBMD, reduced BTM, and appeared to be safe in hemodialysis patients with osteoporosis. © 2019 American Society for Bone and Mineral Research.

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.

Bone turnover markers to explain changes in lumbar spine BMD with abaloparatide and teriparatide: results from ACTIVE

SummaryEarly PINP changes correlate with 18-month lumbar spine BMD changes and the correlation was greater with abaloparatide versus teriparatide. The uncoupling index was similar between the two agents.IntroductionWe evaluated the relationship between early PINP changes and subsequent changes in spine BMD following abaloparatide and teriparatide treatments. We also explored the use of an “uncoupling index” (UI), the balance between bone formation and bone resorption, which we hypothesised would be similar in response to these treatment groups.MethodsBlood samples were taken for measurement of bone turnover markers (BTMs) s-PINP and s-CTX at baseline, 1, 3, 6, 12, and 18 months from 189 abaloparatide patients and 227 teriparatide patients randomly selected from all participants who completed the study. BMD was measured by DXA at baseline, 6, 12, and 18 months. Correlations were calculated between log ratio of BTMs from baseline to 3 months and percent change from baseline in BMD at 18 months. A UI was calculated using log transformation and subtraction of the standard deviate for s-CTX from the standard deviate for s-PINP for each patient.ResultsEarly BTM changes were associated with subsequent BMD changes for both treatments. Pearson correlations for the log ratio of PINP over baseline at 3 months and BMD percent change from baseline at 18 months were larger (P < 0.0001) with abaloparatide (r = 0.561) than teriparatide (r = 0.198). The mean UI at 1 month was greater for abaloparatide versus teriparatide (1.743 and 1.493, respectively; P = 0.03) but was similar at 3 months or later time points.ConclusionsEarly s-PINP changes correlate with percentage change in lumbar spine BMD 18 months after treatment with both abaloparatide and teriparatide, though the correlation with abaloparatide was greater. The UI was similar between abaloparatide and teriparatide suggesting that the balance between formation and resorption markers was similar.

Follow-Up of Bone Mineral Density Changes in de novo Kidney Transplant Recipients Treated with Two Doses of the Receptor Activator of Nuclear Factor κB Ligand Inhibitor Denosumab

Background: Studies in women with post-menopausal osteoporosis have shown that discontinuation of treatment with denosumab leads to an increased risk of vertebral fractures because of rebound bone turnover and rapid loss of bone mineral density (BMD). Methods: In a post hoc analysis of the Prolia for Osteoporosis of Transplant Operated Patient study, we analyzed the effect of denosumab withdrawal on BMD changes. Twenty-five de novo kidney transplant recipients (KTR) who were treated for 1 year with 2 six-monthly doses of denosumab on top of standard treatment (daily calcium and vitamin D) were compared to a control group of 29 KTR who received standard treatment alone. BMD changes were analyzed by repeated dual-energy X-ray absorptiometry shortly after transplantation (baseline), after 6 and 12 months (active treatment phase) and after 2–6.5 years (follow-up phase). Results: The average BMD at the lumbar spine declined markedly after discontinuation of treatment with denosumab but increased again thereafter. Thus, the average monthly change in lumbar spine BMD from month 12 onward was only 0.1 ± 2.8‰ in the denosumab group but 1.5 ± 1.9‰ in the control group (p = 0.021). The average monthly change in lumbar spine BMD from baseline to follow-up was similar in the control and denosumab group (1.1 ± 1.2‰ vs. 1.5 ± 2.4‰, p = 0.788). Similar results were seen at the total hip. Conclusions: In de novo KTR treated with 2 doses of denosumab, we detect a marked decrease in lumbar spine and hip BMD when denosumab is discontinued. Denosumab treatment should therefore not be discontinued without considering an alternative antiresorptive treatment.

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.

Denosumab effects on bone density and turnover in postmenopausal women with low bone mass with or without previous treatment.

Prior osteoporosis therapies may affect the skeletal response to denosumab. We compared the effect of denosumab (60 mg every 6 months for 12 months) on bone mineral density and bone metabolism parameters in postmenopausal women with low bone mass who were either treatment-naïve (n = 30), or previously treated either with zoledronic acid (n = 30), or teriparatide (n = 22). We assessed lumbar spine bone mineral density (BMD) and measured serum concentrations of the bone turnover markers pro-collagen type 1 N-terminal propeptide (PINP) and C-terminal-cross-linking telopeptide of type 1 collagen (CTX), as well as sclerostin, dickkopf-1 (Dkk-1), and myostatin. Lumbar spine BMD increased equivalently in all three groups after 12 months of denosumab compared to baseline (p < 0.001). Serum PINP and CTX decreased significantly with denosumab in pre-treated women reaching the same nadir levels as in treatment-naïve patients (p < 0.001). Women pre-treated with teriparatide displayed lower baseline myostatin concentrations as compared to the other two groups (p < 0.001). Changes in lumbar spine BMD in teriparatide pre-treated women correlated with changes in bone turnover markers and myostatin. Denosumab induced similar increases in lumbar spine BMD in treatment-naïve and pre-treated patients and suppressed serum PINP and CTX to the same levels regardless of prior treatments. In teriparatide pre-treated patients the magnitude of change in bone turnover markers is associated with BMD response.

HIV Infection Is Associated With Abnormal Bone Microarchitecture: Measurement of Trabecular Bone Score in the Women's Interagency HIV Study.

We compared skeletal microarchitecture using trabecular bone score (TBS) and evaluated relationships between change in TBS and lumbar spine (LS) bone mineral density (BMD) in women with and without HIV. Dual-energy X-ray absorptiometry was performed on 319 women with HIV and 118 without HIV in the Women's Interagency HIV Study at baseline and 2 and 5 years, to measure regional BMD and lean and fat mass. TBS was extracted from LS dual-energy X-ray absorptiometry images and examined continuously and categorically [normal (≥1.35), intermediate (1.20-1.35), or degraded (≤1.20) microarchitecture]. Pearson correlation and linear regression examined associations of TBS with regional BMD at baseline and over time. Women with HIV were older (43 vs. 37 years), more likely to be postmenopausal (27% vs. 4%), have lower baseline total fat mass, trunk fat, and leg fat than uninfected women, degraded microarchitecture (27% vs. 9%, P = 0.001), and lower baseline mean TBS (1.3 ± 0.1 vs. 1.4 ± 0.1, P < 0.001). After adjusting for age, race, menopause status, and body mass index, TBS remained lower in women with HIV (P < 0.0001). Annual change in TBS correlated with LS BMD change among women with HIV (r = 0.36, P < 0.0001) and without HIV (r = 0.26, P = 0.02); however, mean % annual TBS change did not differ by HIV status (-1.0%/yr ± 2.9% for HIV+ vs. -0.8%/yr ± 1.7% for HIV-, P = 0.42). Women with HIV have worse bone microarchitecture than uninfected women, but annual percent change in LS BMD or TBS was similar. Use of TBS as an adjunct to BMD to improve prediction of fragility fractures in women with HIV merits further study.

Effect of denosumab on bone mineral density in Japanese women with osteopenia treated with aromatase inhibitors for breast cancer: subgroup analyses of a Phase II study.

BackgroundThe aim of the study was to conduct subgroup analyses of therapeutic effects of 12-month denosumab therapy on the percentage change in bone mineral density (BMD) from baseline in the lumber spine and femoral neck.Materials and methodsWe prospectively evaluated the BMD of the lumbar spine and femoral neck of 100 hormone receptor-positive, clinical stage I–IIIA postoperative postmenopausal breast cancer patients, for whom treatment with aromatase inhibitors (AIs) as adjuvant endocrine therapy was scheduled. The primary endpoint was the percent change in lumbar spine BMD from baseline to 12 months. Patient subgroups were analyzed according to baseline variables that are known risk factors for bone loss, including previous AI therapy, age, time since menopause, baseline body mass index (BMI), and baseline BMD T-score.ResultsAt 12 months, lumbar spine BMD increased by 4.7%; the patients who were administered AI therapy prior to denosumab (n=70) demonstrated a 4.7% increase in BMD, and the patients who received denosumab at the start of AI therapy (n=30) demonstrated a 4.5% increase in BMD (p=0.8385). Additionally, 2.4% and 1.4% increases in BMD of the right and left femoral neck, respectively, were observed. Initiation of AI (with denosumab, before denosumab), type of AI (non-steroidal, steroidal), age (<65, ≥65 years), time since menopause (≤5, >5 years), BMI (<25, ≥25 kg/m2), and T-score (≤−1.0, >−1.0) of the right femoral neck were as follows: (2.2%, 2.5%, p=0.7773), (2.6%, 0.9%, p=0.1726), (2.5%, 2.3%, p=0.7594), (2.1%, 2.4%, p=0.2034), (2.1%, 2.9%, p=0.2034), and (2.3%, 2.7%, p=0.6823), respectively. Initiation of AI (with denosumab, before denosumab), type of AI (non-steroidal, steroidal), age (<65, ≥65 years), time since menopause (≤5, >5 years), BMI (<25, ≥25 kg/m2), and T-score (≤−1.0, >−1.0) of the left femoral neck were as follows: (1.0%, 1.5%, p=0.1972), (1.2%, 2.7%, p=0.2931), (1.4%, 1.3%, p=0.8817), (−0.1%, 1.6%, p=0.1766), (1.3%, 1.9%, p=0.6465), and (1.5%, 1.1%, p=0.6573), respectively.ConclusionTwice-yearly treatment with denosumab was associated with increased BMD among Japanese women receiving adjuvant AI therapy, regardless of the baseline characteristics or skeletal site.

Alcohol Consumption and Bone Mineral Density in People with HIV and Substance Use Disorder: A Prospective Cohort Study.

People living with HIV (PLWH) commonly have low bone mineral density (BMD) (low bone mass and osteoporosis) and are at high risk for fractures. Fractures and low BMD are significant causes of morbidity and mortality, increasingly relevant as PLWH age. Alcohol use is common among PLWH and known to affect bone health. The association between alcohol use and changes in BMD among PLWH is not well understood. We conducted a 3.5-year prospective cohort study of 250 PLWH with substance use disorder or ever injection drug use. Annual alcohol consumption was measured as a mean of grams per day of alcohol, mean number of heavy drinking days per month, mean number of days abstinent per month, and any heavy drinking, using the 30-day Timeline Followback method twice each year. The primary outcome was annual change in BMD measured each year by dual energy X-ray absorptiometry in grams per square centimeter (g/cm2 ) at the femoral neck. Additional dependent variables included annual change in total hip and lumbar spine BMD, >6% annual decrease in BMD at any site, and incident fractures in the past year. Regression models adjusted for relevant covariates. The median age of participants was 50years. The median duration of HIV infection was 16.5years and the mean time since antiretroviral therapy initiation was 12.3years. At study entry, 67% of participants met criteria for low BMD (46% low bone mass, 21% osteoporosis). Median follow-up was 24months. We found no significant associations between any measure of alcohol consumption and changes in BMD (g/cm2 ) at the femoral neck (adjusted β for g/d of alcohol=-0.0032, p=0.7487), total hip, or lumbar spine. There was no significant association between any measure of alcohol consumption and >6% annual decrease in BMD at any site, or incident fractures. In this sample of PLWH and substance use disorders or ever injection drug use, we detected no association between any of the alcohol measures used in the study and changes in BMD or incident fractures.

Patient satisfaction and efficacy of switching from weekly bisphosphonates to monthly minodronate for treatment and prevention of glucocorticoid-induced osteoporosis in Japanese patients with systemic rheumatic diseases: a randomized, clinical trial.

Osteoporosis and associated fractures are major concerns for patients with systemic rheumatic diseases on long-term glucocorticoid therapy. Bisphosphonates increase bone mineral density (BMD) and reduce the frequency of vertebral fractures, but they are associated with poor adherence. The effects of monthly oral minodronate on patients' satisfaction, BMD, and bone turnover markers were investigated in patients with systemic rheumatic diseases on glucocorticoids and weekly oral alendronate or risedronate. Study patients with systemic rheumatic diseases on oral glucocorticoids and weekly alendronate 35mg or risedronate 17.5mg were randomly assigned either to switch to minodronate 50mg every 4weeks or to continue the currently taking weekly bisphosphonate for 52weeks after a 24-week run-in period.Patients were stratified by hospital site, sex, and menopausal status in women at enrollment. The primary endpoint was the difference between the proportions of patients who responded very satisfactory or satisfactory for the current bisphosphonate therapy at weeks 48 and 76 between the two groups. Secondary endpoints included percentage changes in lumbar spine BMD and bone turnover markers from the time of starting allocated treatment. Monthly minodronate was superior to weekly alendronate or risedronate for patients' satisfaction, the increase of lumbar spine BMD, and suppression of serum tartrate-resistant acid phosphatase 5b at week 76. Monthly minodronate is more acceptable and may be more effective than weekly alendronate or risedronate for prevention and treatment of bone loss in patients with systemic rheumatic diseases on glucocorticoid therapy.