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Bone-building drugs

Placebo-controlled trials and meta-analyses found teriparatide, abaloparatide and romosozumab cut new spine fractures by about 70 to 86% in postmenopausal women with osteoporosis. Teriparatide and romosozumab also lowered fractures more than an oral bisphosphonate in head-to-head trials. Romosozumab carries a boxed warning after more heart attacks and strokes than alendronate. Teriparatide's osteosarcoma warning was removed in 2020.

Add to Bio HackChecked 2026-11-14
Status
Prescription drugs in the US, all injected under the skin. Teriparatide (Forteo, 20 mcg daily) is FDA-approved for postmenopausal women with osteoporosis at high risk for fracture, to increase bone mass in men with primary or hypogonadal osteoporosis, and for osteoporosis from long-term steroid medicines. Abaloparatide (Tymlos, 80 mcg daily) is approved for postmenopausal women with osteoporosis at high risk for fracture and to increase bone density in men with osteoporosis. Romosozumab (Evenity, 210 mg monthly for 12 doses) is approved for postmenopausal women with osteoporosis at high risk for fracture and carries an FDA boxed warning for heart attack, stroke and cardiovascular death. FDA removed teriparatide's boxed warning for osteosarcoma in November 2020.
Also called
anabolic osteoporosis drugs, teriparatide, Forteo, Bonsity, PTH 1-34, parathyroid hormone analog, abaloparatide, Tymlos, PTHrP analog, romosozumab, romosozumab-aqqg, Evenity, sclerostin inhibitor
Taken for
osteoporosis, severe osteoporosis, preventing fractures, spine fracture, hip fracture, building bone, bone density, osteoporosis from steroids, osteoporosis in men

Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on

Shown to help7

Reported risks7

What people take it for, and what was found

Shown to help7

StrongStudied in women

Teriparatide: fractures against placebo

Shown to cut new spine fractures by about 65 to 70% and other fractures by about 38 to 53% against placebo in postmenopausal women with osteoporosis.

Compared with placebo injections [1][2]; placebo, in a network of trials [3]

The numbers and sources
Effect
In the pivotal trial, new spine fractures occurred in 14% on placebo and 5% on teriparatide 20 mcg daily under the skin (RR 0.35, 95% CI 0.22 to 0.55) over a median 21 months. Nonvertebral fragility fractures fell from 6% to 3% (RR 0.47). Spine bone density rose 9 percentage points more than placebo [1]. Pooling trials, teriparatide lowered spine fractures (RR 0.30, 95% CI 0.21 to 0.44, 3 trials) and nonvertebral fractures (RR 0.62, 95% CI 0.44 to 0.87, 3 trials) [2]. A network meta-analysis of 107 trials found lower spine and nonvertebral fractures against placebo, among the largest relative reductions [3].
Population
1,637 postmenopausal women with past spine fractures [1]; 2,388 women in 8 RCTs [2]; 193,987 postmenopausal women in 107 trials [3].
Sources
[1], [2], [3]
Caveats
The pivotal trial is part of the pooled reviews [2].
StrongStudied in women

Abaloparatide: fractures against placebo

Shown to cut new spine fractures by 86%, from 4.2% to 0.6% over 18 months, and other fractures by 43% against placebo in postmenopausal women with osteoporosis.

Compared with placebo injections [4][5][6]; placebo, in a network of trials [3]

The numbers and sources
Effect
In ACTIVE, new spine fractures occurred in 0.6% on abaloparatide 80 mcg daily under the skin and 4.2% on placebo at 18 months, an absolute drop of 3.6%. Nonvertebral fractures were 2.7% against 4.7% (43% lower) [4][5]. Pooling 8 RCTs, spine fractures were lower than in controls (RR 0.13, 95% CI 0.06 to 0.26), with adverse events no different from placebo (RR 1.03) [6]. The network meta-analysis found lower spine and nonvertebral fractures against placebo [3].
Population
2,463 women, mean age 69, 1,901 of whom completed ACTIVE [4]; 3,705 postmenopausal women in 8 RCTs [6]; 107 trials [3].
Sources
[4], [5], [6], [3]
Caveats
Most pooled fracture data come from ACTIVE [6].
Strong

Romosozumab: fractures against placebo

Shown to cut new spine fractures by 73% against placebo after 12 months, from 1.8% to 0.5%, in postmenopausal women with osteoporosis.

Compared with placebo injections, followed by denosumab in both groups [7]; placebo or other drugs, pooled [8][9]; placebo, in a network of trials [3]

The numbers and sources
Effect
In FRAME, new spine fractures at 12 months occurred in 0.5% on romosozumab 210 mg monthly under the skin and 1.8% on placebo. Clinical fractures were 1.6% against 2.5% (36% lower). Nonvertebral fractures did not differ significantly (1.6% against 2.1%). After both groups moved to denosumab, spine fractures at 24 months were 0.6% against 2.5% [7]. Pooling trials, spine fractures were less likely than in controls at 12 months (OR 0.42, 95% CI 0.20 to 0.89) [8]. A second review of 9 RCTs found fewer fractures against placebo, alendronate and teriparatide [9]. The network meta-analysis found lower hip, nonvertebral and spine fractures against placebo [3].
Population
7,180 postmenopausal women with a T-score of -2.5 to -3.5 [7]; 13,507 participants, 637 of them men, in 14 studies [8]; 12,796 postmenopausal women in 9 RCTs [9]; 107 trials [3].
Sources
[7], [8], [9], [3]
Caveats
Both groups moved to denosumab after 12 months, so the 24-month result reflects the sequence [7]. The abstract of [9] gives no fracture effect sizes.
ModerateStudied in women

Teriparatide against oral bisphosphonates

Shown to cut new spine fractures by 56% against weekly risedronate, 5.4% against 12.0%, in women with severe osteoporosis. A review of 23 trials agreed.

Compared with oral risedronate, double-dummy [10]; bisphosphonates [11]

The numbers and sources
Effect
In VERO, new spine fractures at 24 months occurred in 5.4% on teriparatide 20 mcg daily and 12.0% on risedronate 35 mg weekly (RR 0.44, 95% CI 0.29 to 0.68). Clinical fractures were 4.8% against 9.8% (HR 0.48). Nonvertebral fragility fractures were 4.0% against 6.1% (HR 0.66, 95% CI 0.39 to 1.10, not significant) [10]. Across 23 head-to-head trials in people not treated with bisphosphonates before, teriparatide lowered fractures (RR 0.61, 95% CI 0.51 to 0.74) [11].
Population
1,360 postmenopausal women with at least two moderate or one severe spine fracture [10]; 6,680 patients in 23 RCTs [11].
Sources
[10], [11]
Caveats
Nonvertebral fractures did not differ significantly in VERO [10].
LimitedStudied in women

Romosozumab against alendronate

One trial found 48% fewer new spine fractures and 38% fewer hip fractures with romosozumab then alendronate than with alendronate alone, in women with osteoporosis and past fractures.

Compared with weekly oral alendronate [12]

The numbers and sources
Effect
Over 24 months, new spine fractures occurred in 6.2% on romosozumab for 12 months then alendronate and 11.9% on alendronate throughout. Clinical fractures were 9.7% against 13.0%, nonvertebral fractures 8.7% against 10.6%, and hip fractures 2.0% against 3.2% [12].
Population
4,093 postmenopausal women with osteoporosis and a fragility fracture [12].
Sources
[12]
Caveats
One trial. Serious cardiovascular events were higher on romosozumab (see Risks) [12].
Why limited
This rests on one trial, of 4,093 people. Strength counts independent studies that agree, so one trial is limited at any size.
Limited

Steroid-induced osteoporosis: teriparatide against alendronate

One trial found fewer new spine fractures with teriparatide than with daily alendronate, 0.6% against 6.1%, in people on long-term steroid medicines.

Compared with daily oral alendronate [13]

The numbers and sources
Effect
Over 18 months, spine bone density rose 7.2% on teriparatide 20 mcg daily and 3.4% on alendronate 10 mg daily. New spine fractures occurred in 0.6% against 6.1%. Nonvertebral fractures did not differ (5.6% against 3.7%). More people on teriparatide had at least one raised calcium reading [13].
Population
428 women and men aged 22 to 89 on at least 5 mg prednisone equivalent for 3 months or more [13].
Sources
[13]
Caveats
Fractures were a secondary outcome in a small trial [13].
ModerateStudied in women

Abaloparatide against teriparatide

Shown to raise hip bone density about 1.5% more than teriparatide in postmenopausal women, with half the high calcium. Fracture data were too few to compare.

Compared with teriparatide injections [14][4]

The numbers and sources
Effect
Pooling head-to-head trials, abaloparatide raised femoral neck density 1.58% (95% CI 0.52 to 2.63) and total hip density 1.46% more than teriparatide at 24 weeks, high-quality evidence. Spine density did not differ. High calcium was 51% less common, and serious adverse events and deaths did not differ. Fracture data were insufficient [14]. In ACTIVE, high calcium occurred in 3.4% on abaloparatide and 6.4% on open-label teriparatide [4].
Population
4 studies with 16 subgroups of postmenopausal women [14]; 1,642 women on abaloparatide or teriparatide in ACTIVE [4].
Sources
[14], [4]
Caveats
All head-to-head trials were sponsored by the maker of abaloparatide [14]. Teriparatide was open-label in ACTIVE [4].

Doses studied

Teriparatide trials and the Forteo label use 20 mcg under the skin once daily [1][15]. The pivotal trial also tested 40 mcg [1]. ACTIVE and the Tymlos label use abaloparatide 80 mcg under the skin once daily, for 18 months in the trial [4][5]. Romosozumab trials and the Evenity label use 210 mg under the skin once a month, given as two injections, for 12 doses, followed by denosumab in FRAME and alendronate in ARCH [7][12][16]. The Tymlos label states it was not evaluated beyond 2 years and advises against longer use in a lifetime [5]. The Forteo label states use beyond 2 years is considered only if fracture risk stays high [15].

Risks

Reported risks6

ModerateVery common

High calcium and uric acid

Shown to raise blood calcium briefly after doses in 11% of women on teriparatide against 2% on placebo, and uric acid above normal in 25% on abaloparatide against 6%.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
At least one episode of high calcium 4 to 6 hours after a dose occurred in 11% of women and 6% of men on teriparatide, against 2% and 0% on placebo, confirmed on repeat testing in 3% and 1%. Uric acid rose above normal in 3% against 1%, without more gout [15]. On abaloparatide, high calcium 4 hours after a dose occurred in 3% against 0.1% on placebo, and uric acid above normal in 25% against 6% [5]. On romosozumab, low calcium was as common as in controls (0.2% each) [16].
Population
Teriparatide and abaloparatide trial participants [15][5]; women in the romosozumab trials [16].
Sources
[15], [5], [16]
Caveats
Pre-dose calcium returned to baseline in both drugs' trials [15][5].
ModerateCommon

FDA boxed warning: heart attack, stroke and cardiovascular death with romosozumab

The label warns romosozumab may raise heart attack, stroke and cardiovascular death. Against alendronate these events were 2.0% against 1.1% in year one.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
The Evenity label carries a boxed warning and states it is not to be started within a year of a heart attack or stroke. In the alendronate-controlled trial, adjudicated major cardiac events (cardiovascular death, nonfatal heart attack, nonfatal stroke) occurred in 2.0% on romosozumab and 1.1% on alendronate (HR 1.87, 95% CI 1.11 to 3.14). Heart attack was 0.8% against 0.2% and stroke 0.6% against 0.3%. In the placebo-controlled trial, these events were 0.8% in each group (HR 1.03, 95% CI 0.62 to 1.72) [16]. Serious cardiovascular events were 2.5% against 1.9% on alendronate [12].
Population
4,054 women in the alendronate-controlled trial and 7,180 in the placebo-controlled trial [16][12].
Sources
[16], [12]
Caveats
Against placebo, events did not differ. The reason for the difference against alendronate is not established.
ModerateCommon

Dizziness, nausea and low blood pressure on standing

Shown to raise dizziness, 8.0% against 5.4%, and nausea, 8.5% against 6.7%, on teriparatide against placebo. Blood pressure drops on standing were slightly more common on abaloparatide.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
On teriparatide, dizziness occurred in 8.0% against 5.4% on placebo, nausea in 8.5% against 6.7%, leg cramps in 2.6% against 1.3% and fainting in 2.6% against 1.4%. Brief symptomatic drops in blood pressure on standing occurred in 5% of healthy volunteers, mostly within the first few doses [15]. On abaloparatide, a blood pressure drop on standing 1 hour after the first injection occurred in 4% against 3% on placebo, and fast heart rate in 2% against 1% [5].
Population
Teriparatide and abaloparatide trial participants and volunteers [15][5].
Sources
[15], [5]
Caveats
Label tables [15][5].
ModerateCommon

Injection-site and allergic reactions with romosozumab

Shown to raise injection-site reactions, 4.9% against 2.8% in controls. Allergic reactions were equally common, 6.5% in each group.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
Across both trials, injection-site reactions occurred in 4.9% on romosozumab and 2.8% on control, mostly pain (1.7% against 1.3%) and redness (1.4% against 0.3%). Allergic reactions occurred in 6.5% in each group, including rare angioedema [16]. A review of 9 RCTs also found higher allergic and injection-site reaction risks [9].
Population
Women in the placebo- and alendronate-controlled trials [16]; 12,796 women in 9 RCTs [9].
Sources
[16], [9]
Caveats
The two sources differ on allergic reactions [16][9].
LimitedRare

Jaw osteonecrosis and atypical thigh fractures with romosozumab

Case reports: a handful of jaw osteonecrosis and atypical thigh fracture cases occurred in the two large romosozumab trials.

The numbers and sources
How common
Rare: fewer than 1 in 1,000 people.
Effect
In FRAME, one atypical femoral fracture and two jaw osteonecrosis cases occurred on romosozumab [7]. In ARCH, during open-label alendronate, jaw osteonecrosis occurred once in each group and atypical femoral fractures 2 and 4 times [12]. The label states one jaw osteonecrosis case occurred during treatment across both trials [16].
Population
7,180 women [7]; 4,093 women [12]; both trials [16].
Sources
[7], [12], [16]
Caveats
Too few events to compare with control.
LimitedHow often is not known

Interaction with digoxin

The label warns that teriparatide's brief rise in blood calcium may predispose people on digoxin to digitalis toxicity.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The Forteo label states transient hypercalcemia may predispose patients to digitalis toxicity. It also lists calciphylaxis reported after approval, with risk factors including kidney failure, warfarin and steroid use. The Tymlos label states no drug interaction studies were done [15][5].
Population
Label statements [15][5].
Sources
[15], [5]
Caveats
A label statement, not a measured rate.

Mixed results1

ModerateHow often is not known

Heart events with romosozumab in pooled trials

Mixed results: one review found a 39% rise in one composite of heart events, and two others found no difference from placebo or controls.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Pooling 6 trials, romosozumab raised four-point major adverse cardiovascular events (RR 1.39, 95% CI 1.01 to 1.90), which lost significance with a random-effects model (RR 1.36, 95% CI 0.99 to 1.87). Three-point events (RR 1.41, 95% CI 0.99 to 2.02) and specific outcomes did not differ [17]. A network meta-analysis of 18 RCTs found no difference from placebo in cardiovascular death or major cardiovascular events [18]. A third review found no difference in cardiovascular events or death against controls [8].
Population
12,219 participants in 6 romosozumab trials [17]; 16,777 postmenopausal women in 18 RCTs [18]; 13,507 participants [8].
Sources
[17], [18], [8]
Caveats
Events were few, and the reviews pool largely the same trials.

Checked, no increase found1

Limited

Osteosarcoma with teriparatide and abaloparatide

FDA removed teriparatide's osteosarcoma boxed warning in November 2020. Both drugs caused osteosarcoma in rats, and US surveillance studies did not find a raised rate in people.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The April 2020 Forteo label carried a boxed warning that teriparatide raised osteosarcoma in rats and was to be prescribed only when benefits outweighed this uncertain risk [19]. The November 2020 label lists the boxed warning as removed [20]. The current label states two US claims-database surveillance studies found three and zero osteosarcoma cases among 379,283 and 153,316 users, a risk similar to comparators, and that cases have been reported rarely after approval [15]. In rats given 3 to 60 times the human exposure for 24 months, osteosarcoma reached 40 to 50% at the highest doses [15]. Abaloparatide also raised osteosarcoma in rats, and the Tymlos label states it is unknown whether it does so in people [5].
Population
Teriparatide users in US claims data, and rats [15][5].
Sources
[19], [20], [15], [5]
Caveats
The surveillance studies could not fully control for confounding, and data beyond 2 years of use are limited [15].

Claims tested and not found

  1. That teriparatide causes osteosarcoma in people. Two US surveillance studies found three and zero cases among 379,283 and 153,316 users, similar to comparators [15].
  2. That romosozumab lowers nonvertebral fractures against placebo within a year. In FRAME, nonvertebral fractures were 1.6% against 2.1% (P = 0.10) [7].

Related

BisphosphonatesDenosumab

Sources

  1. Neer RM, Arnaud CD, Zanchetta JR, et al. Effect of Parathyroid Hormone (1-34) on Fractures and Bone Mineral Density in Postmenopausal Women with Osteoporosis. New England Journal of Medicine. 2001. https://doi.org/10.1056/nejm200105103441904
  2. Han S, Wan S. Effect of teriparatide on bone mineral density and fracture in postmenopausal osteoporosis: meta-analysis of randomised controlled trials. International Journal of Clinical Practice. 2012. https://doi.org/10.1111/j.1742-1241.2011.02837.x
  3. Barrionuevo P, Kapoor E, Asi N, et al. Efficacy of Pharmacological Therapies for the Prevention of Fractures in Postmenopausal Women: A Network Meta-Analysis. The Journal of Clinical Endocrinology & Metabolism. 2019. https://doi.org/10.1210/jc.2019-00192
  4. Miller PD, Hattersley G, Riis BJ, et al. Effect of Abaloparatide vs Placebo on New Vertebral Fractures in Postmenopausal Women With Osteoporosis: A Randomized Clinical Trial. JAMA. 2016. https://doi.org/10.1001/jama.2016.11136
  5. US Food and Drug Administration. Tymlos (abaloparatide injection) prescribing information, revised August 2026. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=712143d9-e21e-4013-bb3b-3426a21060a8
  6. Xu F, Wang Y, Zhu X. The Safety and Efficacy of Abaloparatide on Postmenopausal Osteoporosis: A Systematic Review and Meta-analysis. Clinical Therapeutics. 2024. https://doi.org/10.1016/j.clinthera.2023.12.010
  7. Cosman F, Crittenden DB, Adachi JD, et al. Romosozumab Treatment in Postmenopausal Women with Osteoporosis. New England Journal of Medicine. 2016. https://doi.org/10.1056/nejmoa1607948
  8. Wong RMY, Wong PY, Liu C, et al. Treatment effects, adverse outcomes and cardiovascular safety of romosozumab: existing worldwide data. A systematic review and meta-analysis. Journal of Orthopaedic Translation. 2024. https://doi.org/10.1016/j.jot.2024.07.011
  9. Huang W, Nagao M, Yonemoto N, et al. Evaluation of the efficacy and safety of romosozumab (evenity) for the treatment of osteoporotic vertebral compression fracture in postmenopausal women: A systematic review and meta-analysis of randomized controlled trials (CDM-J). Pharmacoepidemiology and Drug Safety. 2023. https://doi.org/10.1002/pds.5594
  10. Kendler DL, Marin F, Zerbini CAF, et al. Effects of teriparatide and risedronate on new fractures in post-menopausal women with severe osteoporosis (VERO): a multicentre, double-blind, double-dummy, randomised controlled trial. The Lancet. 2018. https://doi.org/10.1016/s0140-6736(17)32137-2
  11. Li M, Ge Z, Zhang B, et al. Efficacy and safety of teriparatide vs. bisphosphonates and denosumab vs. bisphosphonates in osteoporosis not previously treated with bisphosphonates: a systematic review and meta-analysis of randomized controlled trials. Archives of Osteoporosis. 2024. https://doi.org/10.1007/s11657-024-01447-7
  12. Saag KG, Petersen J, Brandi ML, et al. Romosozumab or Alendronate for Fracture Prevention in Women with Osteoporosis. New England Journal of Medicine. 2017. https://doi.org/10.1056/nejmoa1708322
  13. Saag KG, Shane E, Boonen S, et al. Teriparatide or Alendronate in Glucocorticoid-Induced Osteoporosis. New England Journal of Medicine. 2007. https://doi.org/10.1056/nejmoa071408
  14. Hong P, Liu R, Rai S, et al. Is abaloparatide more efficacious on increasing bone mineral density than teriparatide for women with postmenopausal osteoporosis? An updated meta-analysis. Journal of Orthopaedic Surgery and Research. 2023. https://doi.org/10.1186/s13018-023-03595-x
  15. US Food and Drug Administration. Forteo (teriparatide injection) prescribing information, revised August 2026. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aae667c5-381f-4f92-93df-2ed6158d07b0
  16. US Food and Drug Administration. Evenity (romosozumab-aqqg injection) prescribing information, revised August 2026. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=471baba2-7154-4488-9891-0db2f46791e7
  17. Lv F, Cai X, Yang W, et al. Denosumab or romosozumab therapy and risk of cardiovascular events in patients with primary osteoporosis: Systematic review and meta-analysis. Bone. 2020. https://doi.org/10.1016/j.bone.2019.115121
  18. Cheng S, Chu W, Chou W, Chu W, Kang Y. Cardiovascular Safety of Romosozumab Compared to Commonly Used Anti-osteoporosis Medications in Postmenopausal Osteoporosis: A Systematic Review and Network Meta-analysis of Randomized Controlled Trials. Drug Safety. 2025. https://doi.org/10.1007/s40264-024-01475-9
  19. US Food and Drug Administration. Forteo (teriparatide injection) prescribing information, April 2020 version with boxed warning. DailyMed archive, version 33. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=aae667c5-381f-4f92-93df-2ed6158d07b0&version=33
  20. US Food and Drug Administration. Forteo (teriparatide injection) prescribing information, November 2020, boxed warning removed. DailyMed archive, version 34. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=aae667c5-381f-4f92-93df-2ed6158d07b0&version=34

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