abaloparatide and Hip-Fractures

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

This review examines recent literature regarding the clinical management of fragility fractures, provides insight into new practice patterns, and discusses controversies in current management.. There are declining rates of osteoporosis management following initial fragility fracture. Management of osteoporotic fractures via a multidisciplinary team reduces secondary fracture incidence and improves overall osteoporotic care. Anabolic agents (abaloparatide and teriparatide) are effective adjuvants to fracture repair, and have shown positive results in cases of re-fracture in spite of medical management (i.e., bisphosphonates). For AO 31-A1 and A2 intertrochanteric hip fractures (non-reverse obliquity), no clinical advantage of intramedullary fixation over the sliding hip screw (SHS) has been proven; SHS is more cost-effective. As fragility fracture incidence continues to rise, orthopedic surgeons must play a more central role in the care of osteoporotic patients. Initiation of pharmacologic intervention is key to preventing subsequent fragility fractures, and may play a supportive role in initial fracture healing. While the media bombards patients with complications of medical therapy (atypical femur fractures, osteonecrosis of jaw, myocardial infarction), providers need to understand and communicate the low incidence of these complications compared with consequences of not initiating medical therapy.

Topics: Bone Density Conservation Agents; Bone Screws; Diphosphonates; Fracture Fixation; Fracture Fixation, Intramedullary; Fracture Healing; Hip Fractures; Humans; Osteoporotic Fractures; Parathyroid Hormone-Related Protein; Recurrence; Secondary Prevention; Teriparatide

Osteoporosis is characterized by low bone mass and qualitative structural abnormalities of bone tissue, leading to increased bone fragility that results in fractures. Pharmacological therapy is aimed at decreasing the risk of fracture, mainly correcting the imbalance between bone resorption and formation at the level of bone remodeling units. Anabolic therapy has the capability to increase bone mass to a greater extent than traditional antiresorptive agents. The only currently available drug licensed is parathyroid hormone 1-34 (teriparatide); new drugs are on the horizon, targeting the stimulation of bone formation, and therefore improving bone mass, structure and ultimately skeletal strength. These are represented by abaloparatide (a 34-amino acid peptide which incorporates critical N-terminal residues, shared by parathyroid hormone and parathyroid hormone-related protein, followed by sequences unique to the latter protein) and romosozumab (an antibody to sclerostin). In the future, the availability of new anabolic treatment will allow a more extensive utilization of additive and sequential approach, with the goal of both prolonging the period of treatment and, more importantly, avoiding the side effects consequent to long-term use of traditional drugs.

Topics: Accidental Falls; Anabolic Agents; Antibodies, Monoclonal; Drug Combinations; Hip Fractures; Humans; Italy; Osteoporosis; Parathyroid Hormone-Related Protein; Teriparatide

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

Real-world evidence on the comparative effectiveness and safety of abaloparatide versus teriparatide in women with osteoporosis may help inform treatment decisions. Following 18 months of treatment, abaloparatide was comparable to teriparatide for prevention of nonvertebral fractures, resulted in a 22% risk reduction for hip fractures, and demonstrated similar cardiovascular safety. Osteoporotic fracture risk can be reduced with anabolic or antiresorptive medications. In addition to efficacy and safety data from controlled clinical trials, real-world evidence on comparative effectiveness and safety may help inform treatment decisions.. The real-world effectiveness of abaloparatide versus teriparatide on nonvertebral fracture (NVF) incidence and cardiovascular safety during the 19-month period after treatment initiation were evaluated (NCT04974723).. Anonymized US patient claims data from Symphony Health, Integrated Dataverse (IDV)®, May 1, 2017 to July 31, 2019, included women aged ≥ 50 years with ≥ 1 prescription of abaloparatide or teriparatide and no prior anabolic therapy. Most were enrolled in commercial and Medicare health plans. Index was the date of the initial prescription dispensed during the identification period. In 1:1 propensity score matched cohorts, time to first NVF following index date, major adverse cardiovascular events (MACE), and MACE + heart failure (HF) were compared between cohorts using a Cox proportional hazards model.. Propensity score matching yielded 11,616 patients per cohort. Overall median age (interquartile range) was 67 (61, 75) years, and 25.6% had a fracture history. Over 19 months, 335 patients on abaloparatide and 375 on teriparatide had a NVF (hazard ratio [95% confidence interval]: 0.89 [0.77, 1.03]), and 121 and 154 patients, respectively, had a hip fracture [HR (95% CI): 0.78 (0.62, 1.00)]. The MACE and MACE + HF rates were similar between cohorts.. Following 18 months of treatment, abaloparatide was comparable to teriparatide for prevention of NVF and similar cardiovascular safety was demonstrated between cohorts.

Topics: Aged; Bone Density Conservation Agents; Female; Hip Fractures; Humans; Medicare; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Parathyroid Hormone-Related Protein; Postmenopause; Teriparatide; United States