abaloparatide and Spinal-Fractures

Chronic kidney disease (CKD) is an independent risk factor for osteoporosis and is more prevalent among people with CKD than among people who do not have CKD. Although several drugs have been used to effectively treat osteoporosis in the general population, it is unclear whether they are also effective and safe for people with CKD, who have altered systemic mineral and bone metabolism.. To assess the efficacy and safety of pharmacological interventions for osteoporosis in patients with CKD stages 3-5, and those undergoing dialysis (5D).. We searched the Cochrane Kidney and Transplant Register of Studies up to 25 January 2021 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.. Randomised controlled trials comparing any anti-osteoporotic drugs with a placebo, no treatment or usual care in patients with osteoporosis and CKD stages 3 to 5D were included.. Two review authors independently selected studies, assessed their quality using the risk of bias tool, and extracted data. The main outcomes were the incidence of fracture at any sites; mean change in the bone mineral density (BMD; measured using dual-energy radiographic absorptiometry (DXA)) of the femoral neck, total hip, lumbar spine, and distal radius; death from all causes; incidence of adverse events; and quality of life (QoL). Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.. Seven studies involving 9164 randomised participants with osteoporosis and CKD stages 3 to 5D met the inclusion criteria; all participants were postmenopausal women. Five studies included patients with CKD stages 3-4, and two studies included patients with CKD stages 5 or 5D. Five pharmacological interventions were identified (abaloparatide, alendronate, denosumab, raloxifene, and teriparatide). All studies were judged to be at an overall high risk of bias. Among patients with CKD stages 3-4, anti-osteoporotic drugs may reduce the risk of vertebral fracture (RR 0.52, 95% CI 0.39 to 0.69; low certainty evidence). Anti-osteoporotic drugs probably makes little or no difference to the risk of clinical fracture (RR 0.91, 95% CI 0.79 to 1.05; moderate certainty evidence) and adverse events (RR 0.99, 95% CI 0.98 to 1.00; moderate certainty evidence). We were unable to incorporate studies into the meta-analyses for BMD at the femoral neck, lumbar spine and total hip as they only reported the percentage change in the BMD in the intervention group. Among patients with severe CKD stages 5 or 5D, it is uncertain whether anti-osteoporotic drug reduces the risk of clinical fracture (RR 0.33, 95% CI 0.01 to 7.87; very low certainty evidence). It is uncertain whether anti-osteoporotic drug improves the BMD at the femoral neck because the certainty of this evidence is very low (MD 0.01, 95% CI 0.00 to 0.02). Anti-osteoporotic drug may slightly improve the BMD at the lumbar spine (MD 0.03, 95% CI 0.03 to 0.04, low certainty evidence). No adverse events were reported in the included studies. It is uncertain whether anti-osteoporotic drug reduces the risk of death (RR 1.00, 95% CI 0.22 to 4.56; very low certainty evidence).. Among patients with CKD stages 3-4, anti-osteoporotic drugs may reduce the risk of vertebral fracture in low certainty evidence. Anti-osteoporotic drugs make little or no difference to the risk of clinical fracture and adverse events in moderate certainty evidence. Among patients with CKD stages 5 and 5D, it is uncertain whether anti-osteoporotic drug reduces the risk of clinical fracture and death because the certainty of this evidence is very low. Anti-osteoporotic drug may slightly improve the BMD at the lumbar spine in low certainty evidence. It is uncertain whether anti-osteoporotic drug improves the BMD at the femoral neck because the certainty of this evidence is very low. Larger studies including men, paediatric patients or individuals with unstable CKD-mineral and bone disorder are required to assess the effect of each anti-osteoporotic drug at each stage of CKD.

Topics: Antibodies, Monoclonal; Bias; Bone Density; Bone Density Conservation Agents; Denosumab; Female; Femur Neck; Fractures, Spontaneous; Hip; Humans; Indoles; Lumbar Vertebrae; Osteoporosis, Postmenopausal; Parathyroid Hormone-Related Protein; Raloxifene Hydrochloride; Randomized Controlled Trials as Topic; Renal Dialysis; Renal Insufficiency, Chronic; Spinal Fractures; Teriparatide; Thiophenes; Watchful Waiting

Teriparatide (TPTD) and abaloparatide (ABL) are the only osteoanabolic drugs available, at this time, for treatment of osteoporosis. TPTD is a 34-amino acid fragment that is identical in its primary sequence to the 34 amino acids of full-length human parathyroid hormone [hPTH(1-84)]. ABL is identical to parathyroid hormone-related peptide (PTHrP) through the first 22 residues with significantly different amino acids inserted thereafter, between residues 22 and 34. The osteoanabolic actions of PTH are due directly to its effects on cells of the osteoblast lineage and indirectly by stimulating IGF-I synthesis and suppressing sclerostin and associated enhancement of Wnt signalling. Both TPTD and ABL are ligands that bind to and activate the PTH receptor type 1 (PTHR1) receptor but they appear to do so differently: ABL favours the transient, more anabolic configuration of the receptor. Both TPTD and ABL reduce the risk of vertebral fractures and non-vertebral fractures. Both drugs are administered for a maximum of 24 months, and should be followed by an antiresorptive agent to maintain gains in bone mineral density (BMD). Romosozumab, a monoclonal antibody that binds to and inhibits sclerostin, appears to have dual actions by stimulating bone formation and reducing bone resorption. In the pivotal clinical trial, romosozumab, administered as a 210 mg monthly subcutaneous dose, significantly reduced new vertebral fractures and in a subsequent study reduced both vertebral and non-vertebral fractures.

Topics: Animals; Antibodies, Monoclonal; Bone Density; Bone Density Conservation Agents; Bone Remodeling; Drug Therapy, Combination; Humans; Osteoblasts; Osteoporosis; Osteoporotic Fractures; Parathyroid Hormone-Related Protein; Risk Factors; Signal Transduction; Spinal Fractures; Teriparatide; Treatment Outcome

This network meta-analysis assessed the efficacy of abaloparatide versus other treatment options to reduce the risk of fractures in women with postmenopausal osteoporosis. The analysis indicates that abaloparatide reduces the risk of fractures in women with postmenopausal osteoporosis versus placebo and compared with other treatment options.. This network meta-analysis (NMA) assessed the relative efficacy of abaloparatide versus other treatments to reduce the risk of fractures in women with postmenopausal osteoporosis (PMO).. PubMed®, Embase®, and the Cochrane Central Register of Controlled Trials were searched for randomized controlled trials published before December 20, 2017, that included women with PMO who were eligible to receive interventions for primary or secondary fracture prevention. The NMA was conducted by fracture site (vertebral [VF], nonvertebral [NVF], and wrist), with the relative risk (RR) of fracture versus placebo the main clinical endpoint. The NMA used fixed-effects and random-effects approaches.. A total of 4978 articles were screened, of which 22 were included in the analysis. Compared with other treatments, abaloparatide demonstrated the greatest treatment effect relative to placebo in the VF network (RR = 0.13; 95% credible interval [CrI] 0.04-0.34), the NVF network (RR = 0.50; 95% CrI 0.28-0.85), and the wrist fracture network (RR = 0.39; CrI 0.15-0.90). Treatment ranking showed that abaloparatide had the highest estimated probability of preventing fractures in each of the networks (79% for VF, 70% for NVF, and 53% for wrist fracture) compared with other treatments. Individual networks demonstrated a good level of agreement with direct trial evidence and direct pair-wise comparisons.. This NMA indicates that abaloparatide reduces the RR of VF, NVF, and wrist fracture in women with PMO with or without prior fracture versus placebo, compared with other treatment options. Limitations include that adverse events and drug costs were not considered, and that generalizability is limited to the trial populations and endpoints included in the NMA.

Topics: Bone Density Conservation Agents; Female; Hip Fractures; Humans; Network Meta-Analysis; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Parathyroid Hormone-Related Protein; Randomized Controlled Trials as Topic; Risk Reduction Behavior; Spinal Fractures; Wrist Injuries

Skeletal anabolic agents enhance bone formation, which is determined by the number and function of osteoblasts. Signals that influence the differentiation and function of cells of the osteoblast lineage play a role in the mechanism of action of anabolic agents in the skeleton. Wnts induce the differentiation of mesenchymal stem cells toward osteoblasts, and insulin-like growth factor I (IGF-I) enhances the function of mature osteoblasts. The activity of Wnt and IGF-I is controlled by proteins that bind to the growth factor or to its receptors. Sclerostin is a Wnt antagonist that binds to Wnt co-receptors and prevents Wnt signal activation. Teriparatide, a 1-34 amino terminal fragment of parathyroid hormone (PTH), and abaloparatide, a modified 1-34 amino terminal fragment of PTH-related peptide (PTHrp), induce IGF-I, increase bone mineral density (BMD), reduce the incidence of vertebral and non-vertebral fractures and are approved for the treatment of postmenopausal osteoporosis. Romosozumab, a humanized anti-sclerostin antibody, increases bone formation, decreases bone resorption, increases BMD and reduces the incidence of vertebral fractures. An increased incidence of cardiovascular events has been associated with romosozumab, which is yet to be approved for the treatment of osteoporosis. In conclusion, cell and molecular studies have formed the foundation for the development of new anabolic therapies for osteoporosis with proven efficacy on the incidence of new fractures.

Topics: Adaptor Proteins, Signal Transducing; Antibodies, Monoclonal; Bone Density; Bone Density Conservation Agents; Bone Morphogenetic Proteins; Bone Resorption; Genetic Markers; Humans; Insulin-Like Growth Factor I; Osteoblasts; Osteogenesis; Osteoporosis; Osteoporotic Fractures; Parathyroid Hormone-Related Protein; Spinal Fractures; Teriparatide; Wnt Signaling Pathway

The purpose is to review the efficacy and optimal use of parathyroid hormone and parathyroid hormone-related protein analogs in osteoporosis treatment.. The parathyroid hormone analog teriparatide, a potent stimulator of bone remodeling, increases hip and spine bone mineral density and reduces the risk of vertebral and non-vertebral fractures in postmenopausal osteoporotic women. The parathyroid hormone-related protein analog, abaloparatide, also reduces fracture incidence but has pharmacological effects that differ from teriparatide, particularly in cortical bone. These analogs provide maximal benefit when their use is followed by a potent antiresorptive medication. Moreover, studies have shown that the combination of teriparatide and the RANK-ligand inhibitor, denosumab, increase bone density and estimated strength more than monotherapy and more than any currently available regimen. Parathyroid hormone and parathyroid hormone-related protein analogs, whether as monotherapy, in combination with antiresorptive agents or in sequence with antiresorptive agents, will likely play an expanding role in osteoporosis management.

Topics: Bone Density; Bone Density Conservation Agents; Denosumab; Drug Therapy, Combination; Humans; Osteoporosis; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Parathyroid Hormone; Parathyroid Hormone-Related Protein; Spinal Fractures; Teriparatide

The ACTIVE study demonstrated the antifracture efficacy of abaloparatide in postmenopausal women with osteoporosis. ACTIVExtend demonstrated sustained fracture risk reduction with alendronate in abaloparatide-treated participants from ACTIVE. A direct comparison of the efficacy of abaloparatide and antiresorptive therapies has not been performed.. The objective of this analysis is to compare the antifracture efficacy of abaloparatide in ACTIVE with that of alendronate in ACTIVExtend.. In this post hoc analysis, the rate of new vertebral fractures for women in ACTIVExtend (N = 1139) was calculated based on baseline and endpoint radiographs for placebo or abaloparatide in ACTIVE and alendronate in ACTIVExtend. Vertebral fracture rates between abaloparatide and alendronate were compared in a Poisson regression model. Fracture rates for nonvertebral and clinical fractures were compared based on a Poisson model during 18 months of abaloparatide or placebo treatment in ACTIVE and 18 months of alendronate treatment in ACTIVExtend.. The vertebral fracture rate was lower during abaloparatide treatment in ACTIVE (0.47 fractures/100 patient-years) than alendronate treatment in ACTIVExtend (1.66 fractures/100 patient-years) (relative risk reduction 71%; P = .027). Although the comparisons did not meet statistical significance, after switching from placebo (ACTIVE) to alendronate (ACTIVExtend), the rate of new vertebral fractures decreased from 2.49 to 1.66 fractures per 100 patient-years, and after switching from abaloparatide to alendronate from 0.47 to 0.19 fractures per 100 patient-years. The rates of nonvertebral fractures and clinical fractures were not significantly different.. Initial treatment with abaloparatide may result in greater vertebral fracture reduction compared with alendronate in postmenopausal women with osteoporosis.

Topics: Aged; Alendronate; Bone Density; Bone Density Conservation Agents; Drug Therapy, Combination; Female; Femur Neck; Humans; Lumbar Vertebrae; Middle Aged; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Parathyroid Hormone-Related Protein; Placebos; Radiography; Risk Factors; Spinal Fractures; Treatment Outcome

We evaluated the efficacy of abaloparatide in women who were at increased risk for fracture, based on CHMP recommended risk thresholds, at the Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE) study baseline. Among patients at high risk based on FRAX probabilities, 18 months of abaloparatide significantly decreased risk for all fracture endpoints compared with placebo.. Abaloparatide, a novel anabolic agent for the treatment of postmenopausal osteoporosis, significantly reduced the risk of vertebral and nonvertebral fractures in the ACTIVE study compared with placebo. In this post hoc analysis, we evaluated abaloparatide's efficacy in a subset of women in the study at an increased risk of fracture at baseline, based on the Committee for Medicinal Products for Human Use (CHMP) recommended risk thresholds for inclusion in clinical trials.. Women with a baseline 10-year risk of major osteoporotic fracture ≥ 10% or hip fracture ≥ 5%, assessed using the FRAX® tool (including femoral neck bone mineral density), were included in the analysis. The proportion with one or more events of new morphometric vertebral fractures was calculated. Event rates for nonvertebral, major osteoporotic, and all clinical fractures were estimated using Kaplan-Meier analysis.. Following 18 months of treatment, abaloparatide significantly reduced incident vertebral fractures compared with placebo (relative risk reduction = 91%; 0.5% versus 5.6%; p < 0.001). Abaloparatide treatment was also associated with significantly fewer nonvertebral, major osteoporotic, and clinical fractures compared with placebo: 2.7% versus 5.8%, p = 0.036; 1.3% versus 6.0%, p < 0.001; and 3.5% versus 8.2%, p = 0.006, respectively. The effect of abaloparatide on major osteoporotic fractures (78% reduction) was significantly greater than that seen with teriparatide (23% reduction, p = 0.007).. In a subset of postmenopausal women at increased risk of fracture as judged by CHMP guidance, abaloparatide significantly decreased the risk of all fracture endpoints compared with placebo.

Topics: Aged; Bone Density; Bone Density Conservation Agents; Female; Hip Fractures; Humans; Middle Aged; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Parathyroid Hormone-Related Protein; Postmenopause; Risk Factors; Spinal Fractures; Treatment Outcome

Geographic heterogeneity has been observed in fracture risk and efficacy of therapeutic intervention in postmenopausal osteoporosis. The objectives of these analyses were to assess across geographic and ethnic subgroups the heterogeneity of fracture incidence and baseline risk, and consistency of effect of abaloparatide-SC vs placebo on fracture risk reduction in the 18-month, phase 3, multinational, ACTIVE randomized controlled trial. Prespecified exploratory analyses of geographic subgroups (North America, South America, Europe, Asia) and post hoc analyses of ethnic subgroups (Hispanic or Latino, other) of postmenopausal women with osteoporosis enrolled in the abaloparatide-SC and placebo cohorts (n = 1645) were performed. Country-specific FRAX models were used to calculate 10-year absolute fracture risks. Relative risk reductions for vertebral fractures and hazard ratios for non-vertebral, clinical, and major osteoporotic fractures were calculated. Forest plots were constructed to assess treatment-by-subgroup interactions for each geographic region and ethnicity. Baseline prevalence of vertebral fractures was similar across geographies; baseline prevalence of non-vertebral fractures was more variable. Ten-year major osteoporosis fracture and hip fracture risks were variable across and within regions. The effects of abaloparatide-SC on reducing the risk of vertebral, non-vertebral, clinical, and major osteoporotic fractures were similar across regions, and for Hispanic or Latino vs other ethnicities. A limitation was the limited power to detect interactions with few events. In conclusion, despite geographic variability in fracture incidence and risk at baseline, no differences were detected in the effects of abaloparatide-SC in reducing vertebral, non-vertebral, clinical, and major osteoporotic fracture risk across assessed geographic regions and ethnicities.

Topics: Aged; Aged, 80 and over; Bone Density Conservation Agents; Female; Humans; Incidence; Middle Aged; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Parathyroid Hormone-Related Protein; Postmenopause; Spinal Fractures; Treatment Outcome

Advanced age is an important risk factor for fracture. The Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE) trial showed that subcutaneous abaloparatide increased bone mineral density (BMD) and reduced the risk of vertebral and nonvertebral fractures in postmenopausal women with osteoporosis. This study describes the effects of abaloparatide in the subgroup of women aged 80 or more years in ACTIVE.. Post hoc analyses of BMD and fracture incidence in this subgroup of women who received abaloparatide or placebo in the 18-month, phase 3, double-blind, randomized controlled ACTIVE trial.. The mean ages of the women ≥80 years were 81.9 and 81.7 years in the placebo (n = 43) and abaloparatide (n = 51) groups, respectively. The increases in BMD from baseline to 18 months with abaloparatide treatment were 3.9% at the total hip (P < 0.001), 3.6% at the femoral neck (P < 0.01), and 12.1% at the lumbar spine (P < 0.001), and were similar to those observed in the overall population. Abaloparatide therapy was associated with numerical, but not statistically significant, reductions in the risk of vertebral and nonvertebral fractures in this subpopulation, compared with placebo. The proportion of participants reporting adverse events was similar between treatment groups and between the older subgroup and the overall population.. Abaloparatide was effective in increasing BMD in the very elderly subgroup of ACTIVE, with a safety profile similar to that of the overall study population.

Topics: Aged, 80 and over; Bone Density; Bone Density Conservation Agents; Double-Blind Method; Female; Femur Neck; Humans; Incidence; Lumbar Vertebrae; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Parathyroid Hormone-Related Protein; Pelvic Bones; Postmenopause; Risk Factors; Spinal Fractures; Treatment Outcome

In women with postmenopausal osteoporosis, we investigated the effects of 24 months of treatment with alendronate (ALN) following 18 months of treatment with abaloparatide (ABL) or placebo (PBO).. Women who completed ABL or PBO treatment in ACTIVE were eligible to receive up to 24 months of ALN. We evaluated the incidence of vertebral and nonvertebral fractures and changes in bone mineral density (BMD) during the entire 43-month period from ACTIVE baseline to the end of ACTIVExtend and for the 24-month extension only.. Five hundred fifty-eight women from ACTIVE's ABL group and 581 from its PBO group (92% of ABL and PBO completers) were enrolled. During the full 43-month treatment period, 0.9% of evaluable women in the ABL/ALN group experienced a new radiographic vertebral fracture vs 5.6% of women in the PBO/ALN group, an 84% relative risk reduction (RRR, P < 0.001). Kaplan-Meier incidence rates for other reported fracture types were significantly lower for ABL/ALN vs PBO/ALN (all P < 0.05). Gains in BMD achieved during ACTIVE were further increased during ACTIVExtend. For ACTIVExtend only, RRR for vertebral fractures was 87% with ABL/ALN vs PBO/ALN (P = 0.001). Adverse events were similar between groups. A supplemental analysis for regulatory authorities found no hip fractures in the ABL/ALN group vs five in the PBO/ALN group.. Eighteen months of ABL followed by 24 months of ALN reduced the risk of vertebral, nonvertebral, clinical, and major osteoporotic fractures and increased BMD. Sequential ABL followed by ALN appears to be an effective treatment option for postmenopausal women at risk for osteoporosis-related fractures.

Topics: Aged; Aged, 80 and over; Alendronate; Bone Density; Bone Density Conservation Agents; Drug Administration Schedule; Drug Substitution; Female; Femur Neck; Humans; Maintenance Chemotherapy; Middle Aged; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Parathyroid Hormone-Related Protein; Placebos; Spinal Fractures

To assess the efficacy and safety of 18 months of subcutaneous abaloparatide (ABL-SC) or placebo (PBO) followed by 6 months of alendronate (ALN) (preplanned interim analysis).. ACTIVExtend, an extension of ACTIVE, enrolled patients who completed 18 months of ABL-SC or PBO in ACTIVE to receive up to 24 additional months of open-label ALN; there was 1 month between the studies to re-consent patients.. Of 1243 eligible ACTIVE patients, 1139 (92%) were enrolled in ACTIVExtend beginning November 20, 2012. These results are from a prespecified 6-month interim analysis (cutoff date, June 2, 2015); the study is ongoing. Findings indicated percentages of patients with new morphometric vertebral fractures: PBO/ALN, 4.4% vs ABL-SC/ALN, 0.55%; relative risk reduction, 87% (relative risk, 0.13; 95% CI, 0.04-0.41; P<.001). Kaplan-Meier estimated rates of nonvertebral fractures were PBO/ALN, 5.6% vs ABL-SC/ALN, 2.7%; risk reduction, 52% (hazard ratio [HR], 0.48; 95% CI, 0.26-0.89; log-rank P=.02). There was also a 58% risk reduction of major osteoporotic fractures (HR, 0.42; 95% CI, 0.21-0.85; log-rank P=.01) and a 45% risk reduction of clinical fractures (HR, 0.55; 95% CI, 0.33-0.92; log-rank P=.02) in the ABL-SC/ALN group vs the PBO/ALN group. At 25 months, bone mineral density percentage change from ACTIVE baseline for ABL-SC/ALN vs PBO/ALN was as follows: lumbar spine, 12.8%; total hip, 5.5%; femoral neck, 4.5% vs 3.5%, 1.4%, 0.5%, respectively (group differences at all sites P<.001).. Use of ABL-SC for 18 months followed by ALN for 6 months improved bone mineral density and reduced fracture risk throughout the skeleton and may be an effective treatment option for postmenopausal women with osteoporosis.. clinicaltrials.gov Identifier: NCT01657162.

Topics: Aged; Aged, 80 and over; Alendronate; Bone Density; Bone Density Conservation Agents; Female; Humans; Injections, Subcutaneous; Kaplan-Meier Estimate; Middle Aged; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Parathyroid Hormone-Related Protein; Proportional Hazards Models; Spinal Fractures

Additional therapies are needed for prevention of osteoporotic fractures. Abaloparatide is a selective activator of the parathyroid hormone type 1 receptor.. To determine the efficacy and safety of abaloparatide, 80 μg, vs placebo for prevention of new vertebral fracture in postmenopausal women at risk of osteoporotic fracture.. The Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE) was a phase 3, double-blind, RCT (March 2011-October 2014) at 28 sites in 10 countries. Postmenopausal women with bone mineral density (BMD) T score ≤-2.5 and >-5.0 at the lumbar spine or femoral neck and radiological evidence ≥2 mild or ≥1 moderate lumbar or thoracic vertebral fracture or history of low-trauma nonvertebral fracture within the past 5 years were eligible. Postmenopausal women (>65 y) with fracture criteria and a T score ≤-2.0 and >-5.0 or without fracture criteria and a T score ≤-3.0 and >-5.0 could enroll.. Blinded, daily subcutaneous injections of placebo (n = 821); abaloparatide, 80 μg (n = 824); or open-label teriparatide, 20 μg (n = 818) for 18 months.. Primary end point was percentage of participants with new vertebral fracture in the abaloparatide vs placebo groups. Sample size was set to detect a 4% difference (57% risk reduction) between treatment groups. Secondary end points included change in BMD at total hip, femoral neck, and lumbar spine in abaloparatide-treated vs placebo participants and time to first incident nonvertebral fracture. Hypercalcemia was a prespecified safety end point in abaloparatide-treated vs teriparatide participants.. Among 2463 women (mean age, 69 years [range, 49-86]), 1901 completed the study. New morphometric vertebral fractures occurred less frequently in the active treatment groups vs placebo. The Kaplan-Meier estimated event rate for nonvertebral fracture was lower with abaloparatide vs placebo. BMD increases were greater with abaloparatide than placebo (all P < .001). Incidence of hypercalcemia was lower with abaloparatide (3.4%) vs teriparatide (6.4%) (risk difference [RD], −2.96 [95%CI, −5.12 to −0.87]; P = .006). [table: see text].. Among postmenopausal women with osteoporosis, the use of subcutaneous abaloparatide, compared with placebo, reduced the risk of new vertebral and nonvertebral fractures over 18 months. Further research is needed to understand the clinical importance of RD, the risks and benefits of abaloparatide treatment, and the efficacy of abaloparatide vs other osteoporosis treatments.. clinicaltrials.gov Identifier: NCT01343004.

Topics: Aged; Aged, 80 and over; Bone Density; Bone Density Conservation Agents; Double-Blind Method; Female; Femur Neck; Humans; Hypercalcemia; Injections, Subcutaneous; Lumbar Vertebrae; Middle Aged; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Parathyroid Hormone-Related Protein; Pelvic Bones; Placebos; Postmenopause; Radiography; Spinal Fractures; Teriparatide; Thoracic Vertebrae

Topics: Female; Humans; Osteoporosis; Parathyroid Hormone-Related Protein; Postmenopause; Spinal Fractures