Abaloparatide (Tymlos)
Abaloparatide; synthetic human parathyroid hormone-related peptide (PTHrP(1-34)) analog; C174H300N56O49
FDA-approved synthetic PTHrP(1-34) analog that stimulates new bone formation and reduces vertebral (86% RRR) and nonvertebral (43% RRR) fracture risk in postmenopausal women with osteoporosis (PMID 27533157, NCT01343004).
Last updated: 2026-03-09
Safety Summary
In the ACTIVE trial (N=822 abaloparatide, N=820 placebo), the most common adverse reactions (>=2%) were hypercalciuria (11% vs 9%), dizziness (10% vs 6%), nausea (8% vs 3%), headache (8% vs 6%), palpitations (5% vs 0.4%), fatigue (3% vs 2%), upper abdominal pain (3% vs 2%), and vertigo (2% vs 2%). Injection site reactions during the first month: redness 58% vs 28%, edema 11% vs 3%, pain 10% vs 7%. Discontinuation due to adverse events: 10% abaloparatide vs 6% placebo (FDA label NDA208743). In the men's trial (ATOM), common adverse reactions included injection site erythema (13% vs 5%), dizziness (9% vs 1%), arthralgia (7% vs 1%), and injection site swelling (7% vs 0%) (PMID 36190391). Cardiovascular safety analysis showed transient HR increase (mean 7.9 bpm at 1 hour post-dose) that resolves within 4 hours, with no increase in serious cardiac AEs or MACE. Time to first MACE+HF was actually significantly longer with abaloparatide vs placebo (HR 0.30, p=0.02) (PMID 32658264). Anti-drug antibodies developed in 41% of women at 18 months and 25% of men at 12 months, but had no clinically significant impact on efficacy or safety (FDA label NDA208743). A single case report described pseudoxanthoma elasticum (PXE) developing in a genetically predisposed patient (heterozygous ABCC6 mutation) 6 weeks after starting abaloparatide (PMID 40606685).
Known Side Effects
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Who Should NOT Use This
History of systemic hypersensitivity including anaphylaxis, dyspnea, and urticaria (FDA label NDA208743)
Increased baseline risk of osteosarcoma. Abaloparatide caused dose-dependent osteosarcoma in rats at exposures 4-28x human exposure (FDA label NDA208743)
Increased baseline risk of osteosarcoma; not approved in pediatric patients (FDA label NDA208743)
Increased baseline risk of osteosarcoma (FDA label NDA208743). However, preclinical data in breast cancer models suggest abaloparatide does not stimulate growth of bone-disseminated cancer cells (PMID 40584157)
Increased baseline risk of osteosarcoma (FDA label NDA208743)
May exacerbate hypercalcemia. 3% incidence of post-injection hypercalcemia vs 0.1% placebo (FDA label NDA208743)
Abaloparatide may cause hypercalciuria (20% vs 15% placebo for urine Ca:Cr >400 mg/g). Monitor urinary calcium if suspected (FDA label NDA208743)
Safety and efficacy not evaluated beyond 2 years. Use for more than 2 years during a patient's lifetime is not recommended (FDA label NDA208743)
AUC increases 2.1-fold in severe renal impairment (CrCl 15-29 mL/min). No dose adjustment required but monitor for adverse reactions (FDA label NDA208743)
Talk to Your Doctor
Before considering Abaloparatide (Tymlos), discuss it with your healthcare provider. Ask about potential interactions with your current medications, whether it is appropriate for your health conditions, and what monitoring may be needed.
Sources: [1-22]
Evidence Assessment
FDA-approved (NDA208743) since April 2017 for postmenopausal women and since December 2023 for men with osteoporosis. Evidence base includes the pivotal Phase 3 ACTIVE trial (N=2463, NCT01343004; PMID 27533157), ACTIVExtend (N=1139, NCT01657162; PMID 28160873), and the Phase 3 ATOM trial in men (N=228, NCT03512262; PMID 36190391). Multiple independent meta-analyses and systematic reviews confirm efficacy (PMID 41598611). This is a fully approved pharmaceutical with robust multi-trial RCT evidence and long-term follow-up data.
1Effect of Abaloparatide vs Placebo on New Vertebral Fractures in Postmenopausal Women With Osteoporosis: A Randomized Clinical Trial (ACTIVE)NCT01343004PMID 27533157
Miller PD et al. - JAMA (2016) - Phase 3 RCT - N=2463 (824 abaloparatide, 818 teriparatide, 821 placebo)
Abaloparatide 80 mcg/day reduced new vertebral fractures by 86% vs placebo (0.6% vs 4.2%, p<0.0001) and nonvertebral fractures by 43% (2.7% vs 4.7%, p=0.049) at 18 months. Lumbar spine BMD +9.2% vs +0.5% placebo. Also significantly reduced major osteoporotic fractures vs placebo and teriparatide.
Limitations: Open-label teriparatide arm limits some comparisons. 18-month duration; longer-term fracture efficacy inferred from extension study.
2Eighteen Months of Treatment With Subcutaneous Abaloparatide Followed by 6 Months of Treatment With Alendronate in Postmenopausal Women With Osteoporosis: Results of the ACTIVExtend TrialNCT01657162PMID 28160873
Cosman F et al. - Mayo Clinic Proceedings (2017) - Extension study - N=1139 (558 prior abaloparatide, 581 prior placebo)
At 25 months (18 mo abaloparatide + 6 mo alendronate), vertebral fracture RRR was 87% vs placebo/alendronate (0.6% vs 4.4%, p<0.0001). Nonvertebral fracture RRR was 52% (p=0.017). BMD continued to increase with sequential alendronate.
Limitations: Open-label alendronate phase. No teriparatide comparator arm in extension.
3ACTIVExtend: 24 Months of Alendronate After 18 Months of Abaloparatide or Placebo for Postmenopausal OsteoporosisNCT01657162PMID 29800372
Bone HG et al. - Journal of Clinical Endocrinology and Metabolism (2018) - Extension study - N=1139
After 24 months of alendronate following abaloparatide, lumbar spine BMD reached +12.8% above original baseline (vs +3.5% placebo/alendronate). Total hip +5.5% (vs +1.4%). Fracture risk reduction sustained over 43 months total follow-up.
Limitations: No longer blinded during alendronate phase. Participants are self-selected completers from ACTIVE.
4The Efficacy and Safety of Abaloparatide-SC in Men With Osteoporosis: A Randomized Clinical Trial (ATOM)NCT03512262PMID 36190391
Leder BZ et al. - Journal of Bone and Mineral Research (2023) - Phase 3 RCT - N=228 (149 abaloparatide, 79 placebo)
Lumbar spine BMD +8.5% vs +1.2% placebo (treatment difference 7.3%, 99% CI 5.1-9.6, p<0.0001) at 12 months. Total hip +2.1% vs <0.1%, femoral neck +3.0% vs 0.2%. Serious AEs similar (5.4% vs 5.1%).
Limitations: Smaller sample size than ACTIVE. 12-month duration. Not powered for fracture endpoints.
5FDA Label - Tymlos (abaloparatide) injection
Radius Health, Inc. - FDA/NDA208743 (2023) - Regulatory document - Comprehensive
Complete prescribing information including pharmacology, clinical trial data, safety data, and post-marketing surveillance. Updated December 2023 to include male osteoporosis indication.
Limitations: Regulatory document, not peer-reviewed publication.
6Binding Selectivity of Abaloparatide for PTH-Type-1-Receptor Conformations and Effects on Downstream SignalingPMID 26562265
Hattersley G et al. - Endocrinology (2016) - In vitro receptor binding study - In vitro cell-based assays
Abaloparatide binds PTH1R with high selectivity for the RG (G-protein-dependent) conformation over the R0 (G-protein-independent) conformation. This produces transient cAMP signaling that favors bone formation over resorption compared to teriparatide.
Limitations: In vitro study. Clinical relevance of receptor selectivity profiles must be inferred from clinical trial outcomes.
7Cardiovascular Safety of Abaloparatide in Postmenopausal Women With Osteoporosis: Analysis From the ACTIVE Phase 3 TrialNCT01343004PMID 32658264
Cosman F et al. - Journal of Clinical Endocrinology and Metabolism (2020) - Post hoc safety analysis of RCT - N=2460 (safety population from ACTIVE)
Transient HR increase (mean 7.9 bpm at 1h post-dose) resolving within 4 hours. No increase in serious cardiac AEs (1.0% abaloparatide vs 0.9% placebo). MACE+HF was numerically lower: 0.5% abaloparatide vs 1.7% placebo (HR 0.30, 95% CI 0.10-0.91, p=0.02).
Limitations: ACTIVE was not designed or powered for MACE endpoints. Post hoc analysis. Only postmenopausal women studied.
8The Efficacy and Safety of Abaloparatide in Osteoporosis: A Systematic Review and Meta-AnalysisPMID 41598611
Bonifacio M et al. - Journal of Clinical Medicine (2026) - Systematic review and meta-analysis - 9 quantitative evidence sources pooled
Abaloparatide significantly reduced vertebral fractures (RR 0.14, 95% CI 0.06-0.32) and nonvertebral fractures (RR 0.57, 95% CI 0.37-0.89) vs placebo. SUCRA rankings: lumbar spine BMD 94.9%, total hip BMD 60.1%. Mid-range safety profile (all AE SUCRA 33.2%).
Limitations: Limited number of eligible RCTs for some outcomes. Heterogeneity in study designs. Authors noted limited evidence in men and long-term safety.
9Efficacy and safety of abaloparatide, denosumab, teriparatide, oral bisphosphonates, and intravenous bisphosphonates in the treatment of male osteoporosis: a systematic review and Bayesian network meta-analysisPMID 40309441
Chen L, Ji B, Xia C - Frontiers in Endocrinology (2025) - Systematic review and Bayesian network meta-analysis - 18 RCTs, 4392 participants
Abaloparatide and teriparatide significantly superior to other drugs in improving lumbar spine and femoral neck BMD in men. SUCRA rankings: lumbar spine BMD 82.3%, femoral neck BMD 69.8%. Male osteoporosis focus.
Limitations: Network meta-analysis relies on indirect comparisons. Limited direct head-to-head data. Studies spanned 2000-2022 with variable designs.
10Early Effects of Abaloparatide on Bone Formation and Resorption Indices in Postmenopausal Women With OsteoporosisPMID 33434314
Moreira CA et al. - Journal of Bone and Mineral Research (2021) - Open-label single-arm study with bone biopsies - N=23 postmenopausal women (20 completed, 19 evaluable biopsies)
At 3 months, mineralizing surface increased 5.5-fold (cancellous), 5.2-fold (endocortical), 2.8-fold (intracortical), and 12.9-fold (periosteal) vs baseline (all p<0.001). Both modeling-based and remodeling-based formation were stimulated.
Limitations: Small sample size. No placebo control group. Single 3-month timepoint. Open-label. Manufacturer support and employee authorship.
11The effect of abaloparatide on the proximal femur in men with osteoporosis assessed by three-dimensional dual-energy X-ray absorptiometryNCT03512262PMID 40692760
Dhaliwal R et al. - JBMR Plus (2025) - Post hoc 3D-DXA analysis of Phase 3 RCT - ATOM trial participants (149 abaloparatide, 79 placebo)
Abaloparatide significantly increased integral vBMD (+3.7%), trabecular vBMD (+7.0%), cortical thickness (+1.1%), and cortical surface BMD (+1.7%) at 12 months in men (all p<0.0001 vs baseline, p<0.01 vs placebo).
Limitations: Post hoc analysis. 3D-DXA is a modeling technique applied to 2D DXA images, not direct volumetric measurement.
12Comparative effectiveness and cardiovascular safety of abaloparatide and teriparatide in postmenopausal women new to anabolic therapy: A US administrative claims database studyNCT04974723PMID 35524068
Saag KG et al. - Osteoporosis International (2022) - Real-world retrospective cohort study - N=23,232 (11,616 per cohort, propensity-matched)
Over 19 months, abaloparatide was comparable to teriparatide for NVF prevention (HR 0.89, 95% CI 0.77-1.03) and showed a 22% risk reduction for hip fractures (HR 0.78, 95% CI 0.62-1.00). MACE and MACE+HF rates were similar between cohorts.
Limitations: Retrospective claims data. No BMD measurements. Potential for unmeasured confounders.
13Effect of Abaloparatide vs Alendronate on Fracture Risk Reduction in Postmenopausal Women With OsteoporosisPMID 31674644
Cosman F et al. - Journal of Clinical Endocrinology and Metabolism (2020) - Post hoc indirect comparison - N=1139 from ACTIVExtend
Vertebral fracture rate was lower during abaloparatide treatment (0.47/100 patient-years) than alendronate (1.66/100 patient-years), representing 71% relative risk reduction (p=0.027).
Limitations: Post hoc indirect comparison across different trial phases. Different populations and timeframes.
14Effect of abaloparatide on fracture incidence and bone mineral density in postmenopausal women with osteoporosis at highest risk for fractureNCT01343004PMID 39999474
Tough DeSapri K et al. - Menopause (2025) - Post hoc subgroup analysis of Phase 3 RCT - N=2026 (664 abaloparatide, 677 placebo, 685 teriparatide)
In the highest-risk subgroup (>=1 professional society high-risk criteria), abaloparatide reduced vertebral fractures (0.72% vs 4.77%, p<0.0001) and showed numerically lower nonvertebral, clinical, and major osteoporotic fractures vs placebo.
Limitations: Post hoc analysis. Multiple subgroup definitions. Not powered for individual fracture type comparisons.
15Abaloparatide versus teriparatide: a head to head comparison of effects on fracture healing in mouse modelsPMID 30334479
Bernhardsson M et al. - Acta Orthopaedica (2019) - Animal study (mice) - N=120 mice across multiple groups
Both abaloparatide and teriparatide improved fracture healing dose-dependently. At equivalent doses, abaloparatide showed approximately 2.5x potency of teriparatide.
Limitations: Animal study in mice. Dosing ratios differ from clinical practice. Not directly translatable to human fracture healing.
16Abaloparatide effects on BMD in acetabular regions corresponding to DeLee and Charnley zones in women with postmenopausal osteoporosisNCT01343004PMID 40786602
Not specified in source - Not specified in source (2025) - Post hoc analysis of Phase 3 RCT - N=500 (250 abaloparatide, 250 placebo)
Abaloparatide significantly increased acetabular BMD in all three DeLee and Charnley zones at 6 and 18 months vs placebo. Mean BMD increases at 18 months: R1 +8.38%, R2 +7.25%, R3 +9.73%.
Limitations: Post hoc analysis of random subgroup. Clinical significance for arthroplasty outcomes not directly demonstrated.
17Abaloparatide increases bone mass without affecting growth of bone-disseminated cancer cellsPMID 40584157
Not specified in source - Not specified in source (2025) - Preclinical animal study (mice) - Mouse models of triple-negative and ER+ breast cancer
Abaloparatide dramatically increased trabecular bone volume in mice inoculated with breast cancer cells without increasing tumor burden or incidence in bone or soft tissue.
Limitations: Preclinical mouse models only. No human data.
18Phase 1b Evaluation of Abaloparatide Solid Microstructured Transdermal System (Abaloparatide-sMTS) in Postmenopausal Women with Low Bone Mineral DensityNCT04366726PMID 33638863
Not specified in source - Clinical Drug Investigation (2021) - Phase 1b open-label study - N=22 postmenopausal women
Self-administered abaloparatide-sMTS 300 mcg/day to thigh for 29 days. Consistent PK profile: Cmax 447 pg/mL, Tmax 0.33h. sPINP increased 45.4% (Day 15) and 64.4% (Day 29). Self-administration success rate 99.7%.
Limitations: Small sample size. Short duration (29 days). No placebo control. No BMD or fracture endpoints.
19Rapid fracture healing of the greater tuberosity fragment after shoulder hemiarthroplasty in a patient with daily abaloparatide injection: A case reportPMID 41626402
Not specified in source - Not specified in source (2025) - Case report - N=1
64-year-old woman on abaloparatide who developed 4-part shoulder fracture-dislocation. Following hemiarthroplasty, bone union at greater tuberosity achieved by postoperative day 16.
Limitations: Single case report. Cannot establish causation.
20Abaloparatide-induced pseudoxanthoma elasticumPMID 40606685
Not specified in source - JAAD Case Reports (2025) - Case report - N=1
56-year-old woman with heterozygous ABCC6 mutation developed PXE 6 weeks after starting abaloparatide. Genetic predisposition likely unmasked by abaloparatide's effects on calcium homeostasis.
Limitations: Single case report. Patient had pre-existing genetic predisposition.
21ACTIVExtend subgroup analysis: fracture risk reduction and BMD changes by baseline characteristicsNCT01657162PMID 31411768
Cosman F et al. - Not specified in source (2019) - Post hoc subgroup analysis of RCT extension - N=1139
Consistent fracture risk reduction and BMD benefits across subgroups defined by age, years since menopause, presence or absence of prior fracture, and baseline BMD.
Limitations: Post hoc subgroup analyses; not powered for individual subgroup comparisons.
22Number needed to treat analysis of abaloparatide for fracture preventionPMID 29951742
Not specified in source - Not specified in source (2018) - Post hoc analysis / NNT calculation - Derived from ACTIVE trial data
NNT values were favorable compared to other osteoporosis treatments, supporting cost-effectiveness arguments.
Limitations: NNT derived from a single pivotal trial.