abaloparatide
Regulatory sources consulted
Approved indications
- Osteoporosis in postmenopausal women at high fracture risk.
Contraindications
Absolute
- Women of childbearing potential, pregnancy, breastfeeding, hypercalcemia, severe renal impairment, unexplained alkaline phosphatase elevation, osteosarcoma risk, bone cancer, or bone metastases.
Clinical warnings
- Major warning · The first injections require supervision and one hour of observation for orthostatic hypotension, tachycardia, dizziness, palpitations, or nausea. — CIMA/AEMPS, ficha técnica 1221706001
- Major warning · Avoid in patients at risk of osteosarcoma and monitor for hypercalcemia and hypercalciuria. — CIMA/AEMPS, ficha técnica 1221706001
Drug interactions
- HighDigitalis glycosides and vasoactive drugs
Mechanism: Hypercalcemia may promote digitalis toxicity and vasoactive drugs may intensify orthostatic hypotension.
Recommendation: Monitor calcium, ECG, blood pressure, and symptoms.
CIMA/AEMPS, ficha técnica 1221706001
Adverse events
Common (≥1%)
Hypercalciuria, dizziness, back pain, nausea, headache, arthralgia, hypertension, local reaction, and palpitations
Rare but serious
Clinically significant hypercalcemia and anaphylactic reaction
Pregnancy and lactation
Contraindicated in women of childbearing potential, during pregnancy, and during breastfeeding.
Recent literature (PubMed)
Osteoporosis is characterized by low bone mass, increased bone fragility, and increased susceptibility to fracture, which is associated with substantial morbidity, mortality, and economic costs. Worldwide, 1 in 3 women and 1 in 5 men older than 50 years of age experience osteoporotic fractures in their lifetime. Risk factors for osteoporosis include older age, female sex, prior fractures, prior falls, low body weight, history of hip fracture in a parent, glucocorticoid use, cigarette smoking, excess alcohol consumption, certain comorbidities (eg, inflammatory bowel disease, rheumatoid arthritis, and chronic liver and kidney disease), and low level of bone mineral density (BMD; measured by dual-energy x-ray absorptiometry). The fracture risk assessment algorithm combines these clinical risk factors and BMD measurement to estimate the 10-year absolute fracture risk for hip, spine, shoulder, and forearm fractures. For patients at high risk of fracture, such as those with a T score of -2.5 or less (equivalent to a bone mass that is ≥2.5 SDs below that of young adults) for BMD, history of vertebral or hip fracture, multiple fractures, or high 10-year absolute fracture risk (eg, ≥20%), antiresorptive agents (bisphosphonates or, if contraindicated, denosumab) are recommended to reduce vertebral fractures (risk difference, -52 [95% CI, -95 to -18 per 1000 person-years]) and hip fractures (risk difference, -6 [95% CI, -11 to -1 per 1000 person-years]). Anabolic medications (teriparatide, abaloparatide, and romosozumab) should be considered in very high-risk individuals (eg, recent vertebral fractures, hip fracture with a T score of ≤-2.5 for BMD), followed by an antiresorptive agent. The use of fracture liaison services (comprehensive inpatient or outpatient management program for patients after a fracture) was shown to increase medication initiation and adherence by 38% compared with 17% for patients who did not receive fracture liaison services (risk difference, 20% [95% C
The prevalence of osteoporosis is increasing in the United States. To evaluate low bone mass and osteoporosis treatments to prevent fractures. Ovid MEDLINE ALL, Ovid Evidence Based Medicine Reviews: Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and ClinicalTrials.gov from 2014 through February 2022. Adults receiving eligible interventions for low bone mass or osteoporosis. Randomized controlled trials (RCTs) for fracture outcomes, and RCTs and large observational studies (n ≥1000) for harms. Abstracted by 1 reviewer and verified by a second. Independent, dual assessments of risk of bias and certainty of evidence (CoE). We included 34 RCTs (in 100 publications) and 36 observational studies. Bisphosphonates and denosumab reduced hip, clinical and radiographic vertebral, and other clinical fractures in postmenopausal females with osteoporosis (moderate to high CoE). Bisphosphonates for 36 months or more may increase the risk for atypical femoral fractures (AFFs) and osteonecrosis of the jaw (ONJ), but the absolute risks were low. Abaloparatide and teriparatide reduced clinical and radiographic vertebral fractures but increased the risk for withdrawals due to adverse events (WAEs; moderate to high CoE). Raloxifene and bazedoxifene for 36 months or more reduced radiographic vertebral but not clinical fractures (low to moderate CoE). Abaloparatide, teriparatide, and sequential romosozumab, then alendronate, may be more effective than bisphosphonates in reducing clinical fractures for 17 to 24 months in older postmenopausal females at very high fracture risk (low to moderate CoE). Bisphosphonates may reduce clinical fractures in older females with low bone mass (low CoE) and radiographic vertebral fractures in males with osteoporosis (low to moderate CoE). Few studies examined participants with low bone mass, males, or Black-identifying persons, sequential therapy, or treatment beyond 3 years. Bisphosphonates, denosumab, abalopara
Postmenopausal osteoporosis is a chronic progressive disease related to estrogen deficiency at menopause, aging, and superimposed genetic and environmental factors. Many patients with osteoporosis are not diagnosed, and the majority are not treated. Current therapies for osteoporosis include antiresorptive treatments, including bisphosphonates, denosumab, and raloxifene, and osteoanabolic treatments, including teriparatide, abaloparatide, and romosozumab, which is a dual-action agent. Sequential therapies aim to optimize fracture prevention and bone density outcomes for long-term management. Recent guidelines have suggested categorical risk stratification and a goal-directed individualized therapy strategy. New treatments under investigation also hold promise for further improving bone health in postmenopausal osteoporosis.
To review the comparative effectiveness of osteoporosis treatments, including the bone anabolic agents, abaloparatide and romosozumab, on reducing the risk of fractures in postmenopausal women, and to characterise the effect of antiosteoporosis drug treatments on the risk of fractures according to baseline risk factors. Systematic review, network meta-analysis, and meta-regression analysis of randomised clinical trials. Medline, Embase, and Cochrane Library to identify randomised controlled trials published between 1 January 1996 and 24 November 2021 that examined the effect of bisphosphonates, denosumab, selective oestrogen receptor modulators, parathyroid hormone receptor agonists, and romosozumab compared with placebo or active comparator. Randomised controlled trials that included non-Asian postmenopausal women with no restriction on age, when interventions looked at bone quality in a broad perspective. The primary outcome was clinical fractures. Secondary outcomes were vertebral, non-vertebral, hip, and major osteoporotic fractures, all cause mortality, adverse events, and serious cardiovascular adverse events. The results were based on 69 trials (>80 000 patients). For clinical fractures, synthesis of the results showed a protective effect of bisphosphonates, parathyroid hormone receptor agonists, and romosozumab compared with placebo. Compared with parathyroid hormone receptor agonists, bisphosphonates were less effective in reducing clinical fractures (odds ratio 1.49, 95% confidence interval 1.12 to 2.00). Compared with parathyroid hormone receptor agonists and romosozumab, denosumab was less effective in reducing clinical fractures (odds ratio 1.85, 1.18 to 2.92 for denosumab v parathyroid hormone receptor agonists and 1.56, 1.02 to 2.39 for denosumab v romosozumab). An effect of all treatments on vertebral fractures compared with placebo was found. In the active treatment comparisons, denosumab, parathyroid hormone receptor agonists, and romosozumab were
The goal of osteoporosis management is to prevent fractures. Several pharmacological agents are available to lower fracture risk, either by reducing bone resorption or by stimulating bone formation. Bisphosphonates are the most widely used anti-resorptives, reducing bone turnover markers to low premenopausal concentrations and reducing fracture rates (vertebral by 50-70%, non-vertebral by 20-30%, and hip by ~40%). Bisphosphonates bind avidly to bone mineral and have an offset of effect measured in months to years. Long term, continuous use of oral bisphosphonates is usually interspersed with drug holidays of 1-2 years, to minimise the risk of atypical femoral fractures. Denosumab is a monoclonal antibody against RANKL that potently inhibits osteoclast development and activity. Denosumab is administered by subcutaneous injection every 6 months. Anti-fracture effects of denosumab are similar to those of the bisphosphonates, but there is a pronounced loss of anti-resorptive effect from 7 months after the last injection, which can result in clusters of rebound vertebral fractures. Two classes of anabolic drugs are now available to stimulate bone formation. Teriparatide and abaloparatide both target the parathyroid hormone-1 receptor, and are given by daily subcutaneous injection for up to 2 years. Romosozumab is an anti-sclerostin monoclonal antibody that stimulates bone formation and inhibits resorption. Romosozumab is given as monthly subcutaneous injections for 1 year. Head-to-head studies suggest that anabolic agents have greater anti-fracture efficacy and produce larger increases in bone density than anti-resorptive drugs. The effects of anabolic agents are transient, so transition to anti-resorptive drugs is required. The optimal strategy for cycling anabolics, anti-resorptives, and off-treatment periods remains to be determined.