Highlights
- •Bone anabolic therapies (BATs) include teriparatide, abaloparatide and romosozumab.
- •All bone anabolic therapies significantly increase bone mineral density at all locations.
- •All bone anabolic therapies reduce the risk of vertebral fractures.
- •No intervention significantly reduces the risk of non-vertebral fractures.
Abstract
Objective
To systematically evaluate the effects of bone anabolic therapies (BATs) – specifically,
drug therapy with teriparatide, abaloparatide or romosozumab – on fractures, bone
mineral density (BMD), and bone metabolites in postmenopausal osteoporosis.
Methods
Six computerized engines were searched through to November 2018. We selected randomized
controlled trials (RCTs) evaluating the effect of BATs on postmenopausal osteoporosis
and with at least 6 months of follow-up. Controls were placebo, no treatment, or bisphosphonates.
Primary outcomes were vertebral and non-vertebral fractures. Secondary outcomes were:
BMD determined by dual energy X-ray absorptiometry at total hip, lumbar spine, and
femoral neck; N-terminal propeptide of type I procollagen (PINP); C-terminal telopeptide
of type I collagen (CTX); and severe adverse events (SAE). We followed the PRISMA
guidelines for reporting, and used version 2 of the Cochrane risk-of-bias tool. Frequentist
network meta-analyses were performed per outcome. Effects for dichotomous and continuous
outcomes were expressed as relative risks and mean differences and their 95% confidence
intervals. We used p-scores to rank best treatments per outcome.
Results
Sixteen RCTs (n = 18,940) were evaluated. Mean ages ranged between 61 and 74 years,
and follow-up times between 6 and 30 months. Four RCTs (n = 971) excluded patients
with previous fractures. In contrast to placebo/no treatment, all BATs significantly
reduced the risk of vertebral fractures, but no intervention significantly reduced
the risk of non-vertebral fractures; abaloparatide ranked better than other interventions
for both fracture types (p-scores: 0.95, and 0.89, respectively). All BATs significantly
increased BMD at all locations in comparison with placebo/no treatment; romosozumab
consistently ranked better than other interventions at all BMD locations (p-scores
>0.86). Teriparatide ranked better than other interventions for increasing PINP. No
differences in SAE were observed among treatments.
Conclusions
Abaloparatide, romosozumab, and teriparatide are the best treatments, respectively,
to reduce vertebral/non-vertebral fractures, increase BMD, and increase bone formation.
Abbreviations:
95%CIs (95% confidence interval), AP (alkaline phosphatase), BAT (bone anabolic therapy), BMD (bone mineral density), BMI (body mass index), CTX (C-terminal telopeptide of type I collagen), DEXA (dual energy X-ray absorptiometry), HRT (hormone replacement therapy), IU (international unit), MD (mean difference), NMA (network meta-analysis), NTX (crosslinked N-telopeptide of type I collagen), PINP (N-terminal propeptide of type I procollagen), PRISMA (Preferred Reporting Items of Systematic Reviews and Meta-analyses), PTH (parathyroid hormone), RCT (randomized controlled trial), RR (risk ratio), SAE (severe adverse event), SC (subcutaneous), SERM (Selective estrogen receptor modulator)Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to MaturitasAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Clinical practice.Postmenopausal Osteoporosis. N Engl J Med. 2016; 374 (Erratum in: N Engl J Med 374: 1797): 254-262
- Postmenopausal osteoporosis and alendronate.Maturitas. 2004; 48: 179-192
- Treating osteoporosis to prevent fractures: current concepts and future developments.J. Intern. Med. 2019; 285: 381-394
- Pharmacological management of osteoporosis in postmenopausal women: an endocrine society* clinical practice guideline.J. Clin. Endocrinol. Metab. 2019; 104: 1595-1622
- Drug holidays from bisphosphonates and denosumab in postmenopausal osteoporosis: EMAS position statement.Maturitas. 2017; 101: 23-30
- Rebound-associated vertebral fractures after discontinuation of denosumab-from clinic and biomechanics.Osteoporos. Int. 2016; 27: 1917-1921
- Emerging anabolic agents in the treatment of osteoporosis.Expert Opin. Emerg. Drugs. 2017; 22: 247-257
- New therapeutic targets for osteoporosis.Maturitas. 2019; 120: 1-6
- UK clinical guideline for the prevention and treatment of osteoporosis.Arch. Osteoporos. 2017; 12: 43
- Guidelines for the management of osteoporosis and fragility fractures.Intern. Emerg. Med. 2019; 14: 85-102
- The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations.Ann. Intern. Med. 2015; 162: 777-784
- A revised tool for assessing risk of bias in randomized trials.in: Chandler J. McKenzie J. Boutron I. Welch V. Cochrane Methods. Cochrane Database of Systematic Reviews Issue 10. 2016https://doi.org/10.1002/14651858.CD201601 (Suppl 1)
- Conducting indirect-treatment-Comparison and network-meta-Analysis studies: report of the ISPOR task force on indirect treatment comparisons good research practices: part 2.Value Health. 2011; 14: 429-437
- Consistency and inconsistency in network meta-analysis: concepts and models for multi-arm studies.Res. Synth. Methods. 2012; 3: 98-110
- Commentary: heterogeneity in meta-analysis should be expected and appropriately quantified.Int. J. Epidemiol. 2008; 37: 1158-1160
- Head-to-head comparison of risedronate vs. Teriparatide on bone turnover markers in women with postmenopausal osteoporosis: a randomised trial.Int. J. Clin. Pract. 2008; 62: 919-924
- Serum osteoprotegerin and RANKL are not specifically altered in women with postmenopausal osteoporosis treated with teriparatide or risedronate: a randomized, controlled trial.Horm. Metab. Res. 2008; 40: 281-285
- A randomized double-blind trial to compare the efficacy of teriparatide [recombinant human parathyroid hormone (1-34)] with alendronate in postmenopausal women with osteoporosis.J. Clin. Endocrinol. Metab. 2002; 87: 4528-4535
- Effect of intravenous zoledronic acid plus subcutaneous teriparatide [rhPTH(1-34)] in postmenopausal osteoporosis.J. Bone Miner. Res. 2011; 26: 503-511
- Romosozumab treatment in postmenopausal women with osteoporosis.N. Engl. J. Med. 2016; 375: 1532-1543
- Effects of teriparatide, alendronate, or both in women with postmenopausal osteoporosis.J. Clin. Endocrinol. Metab. 2010; 95: 1838-1845
- Romosozumab increases bone mineral density in postmenopausal Japanese women with osteoporosis: a phase 2 study.Bone. 2017; 103: 209-215
- 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.Lancet. 2018; 391 (Erratum in: Lancet 392:2352): 230-240
- Romosozumab (sclerostin monoclonal antibody) versus teriparatide in postmenopausal women with osteoporosis transitioning from oral bisphosphonate therapy: a randomised, open-label, phase 3 trial.Lancet. 2017; 390: 1585-1594
- Effects of abaloparatide, a human parathyroid hormone-related peptide analog, on bone mineral density in postmenopausal women with osteoporosis.J. Clin. Endocrinol. Metab. 2015; 100: 697-706
- Romosozumab in postmenopausal women with low bone mineral density.N. Engl. J. Med. 2014; 370: 412-420
- Effect of abaloparatide vs placebo on new vertebral fractures in postmenopausal women with osteoporosis: a randomized linical trial.JAMA. 2016; 316 (Erratum in: JAMA 2017;317:442): 722-733
- Effect of teriparatide on bone mineral density and biochemical markers in Japanese women with postmenopausal osteoporosis: a 6-month dose-response study.J. Bone Miner. Metab. 2008; 26: 624-634
- Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis.N. Engl. J. Med. 2001; 344: 1434-1441
- Romosozumab or alendronate for fracture prevention in women with osteoporosis.N. Engl. J. Med. 2017; 377: 1417-1427
- Efficacy of teriparatide in increasing bone mineral density in postmenopausal women with osteoporosis--an Indian experience.J. Assoc. Physicians India. 2008; 56: 418-424
- Anabolic effect of estrogen replacement on bone in postmenopausal women with osteoporosis: histomorphometric evidence in a longitudinal study.J. Clin. Endocrinol. Metab. 2001; 86: 289-295
- Five-year changes in bone density, and their relationship to plasma estradiol and pretreatment bone density, in an older population of postmenopausal women using long-term estradiol implants.Gynecol. Endocrinol. 2003; 17: 463-470
- The evolution of selective estrogen receptor modulators in osteoporosis therapy.Climacteric. 2012; 15: 513-523
- Selective estrogen receptor modulators: tissue specificity and clinical utility.Clin. Interv. Aging. 2014; 9: 1437-1452
- Indirect comparison of bazedoxifene vs oral bisphosphonates for the prevention of vertebral fractures in postmenopausal osteoporotic women.Curr. Med. Res. Opin. 2014; 30 (1617-162)
- Denosumab vs bisphosphonates for the treatment of postmenopausal osteoporosis.Eur. J. Endocrinol. 2018; 179: R31-R45
- Denosumab compared to bisphosphonates to treat postmenopausal osteoporosis: a meta-analysis.J. Orthop. Surg. Res. 2018; 13: 194
- Comparison of risk of osteoporotic fracture in denosumab vs alendronate treatment within 3 years of initiation.JAMA Network Open. 2019; 2: e192416
- Drug-related adverse events of osteoporosis therapy.Endocrinol. Metab. Clin. North Am. 2017; 46: 181-192
- Gastric and esophagus events before and during treatment of osteoporosis.Calcif. Tissue Int. 2010; 86: 110-115
- Reports of esophageal cancer with oral bisphosphonate use.N. Engl. J. Med. 2009; 360: 89-90
- Ophthalmological events in patients receiving risedronate: summary of information gained through follow-up in a prescription-event monitoring study in England.Drug Saf. 2006; 29 (151-16)
- Use of oral bisphosphonates and risk of hospital admission with osteonecrosis of the jaw: large prospective cohort study in UK women.Bone. 2019; 124: 69-74
- Long-term drug therapy and drug discontinuations and holidays for osteoporosis fracture prevention: a systematic review.Ann. Intern. Med. 2019; https://doi.org/10.7326/M19-0533
- Drug-related adverse events of osteoporosis therapy.Endocrinol. Metab. Clin. North Am. 2017; 46: 181-192
- Two-thirds of all fractures are not attributable to osteoporosis and advancing age: implication for fracture prevention.J. Clin. Endocrinol. Metab. 2019; 104: 3514-3520
- Factors related to muscle strength in postmenopausal women aged younger than 65 years with normal vitamin D status.Climacteric. 2019; 22: 390-394
- Effects of two training modalities on body fat and insulin resistance in postmenopausal women.J. Strength Cond. Res. 2017; 31: 2955-2964
- Effect of programmed exercise on insulin sensitivity in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials.Menopause. 2017; 24: 1404-1413
- Metabolic syndrome during female midlife: what are the risks?.Climacteric. 2019; 22: 127-132
- Insulin resistance and bone: a biological partnership.Acta Diabetol. 2018; 55: 305-314
- Predictors of metabolic syndrome in community-dwelling older adults.PLoS One. 2018; 13: e0206424
- Osteosarcopenia: where bone, muscle, and fat collide.Osteoporos. Int. 2017; 28: 2781-2790
- Sarcopenia and its association with falls and fractures in older adults: a systematic review and meta-analysis.J. Cachexia Sarcopenia Muscle. 2019; https://doi.org/10.1002/jcsm.12411
- Correction: muscle mass, BMI, and mortality among adults in the United States: a population-based cohort study.PLoS One. 2018; 13 (Erratum in: PLoS One. 2018;13:e0198318): e0198318
- Physical exercise and osteoporosis: effects of different types of exercises on bone and physical function of postmenopausal women.Arq. Bras. Endocrinol. Metabol. 2014; 58: 514-522
- High-intensity interval training improves inflammatory and adipokine profiles in postmenopausal women with metabolic syndrome.Arch. Physiol. Biochem. 2019; 125: 85-91
- Anabolic agents for the treatment of postmenopausal osteoporosis.in: Pérez-López F.R. Postmenopausal Diseases and Disorders. 978-3-030-13935-3 Springer Nature, Basel2019: 387-394
- Abaloparatide for risk reduction of nonvertebral and vertebral fractures in postmenopausal women with osteoporosis: a network meta-analysis.Osteoporos. Int. 2019; 30: 1465-1473
- ACTIVExtend: 24 months of alendronate after 18 months of abaloparatide or placebo for postmenopausal osteoporosis.J Clin EndocrinolMetab. 2018; 103: 2949-2957
- Forsteo, INN-teriparatide - europa.eu.(Accessed March 7)2019
- Bone turnover markers to explain changes in lumbar spine BMD with abaloparatide and teriparatide: results from ACTIVE.Osteoporos. Int. 2019; 30: 667-673
- Effects of 24 months of treatment with romosozumab followed by 12 months of denosumab or placebo in postmenopausal women with low bone mineral density: a randomized, double-blind, phase 2, parallel group study.J. Bone Miner. Res. 2018; 33: 1397-1406
- Screening for osteoporosis to prevent fractures: US preventive services task force recommendation statement.JAMA. 2018; 319: 2521-2531
- Drug efficacies on bone mineral density and fracture rate for the treatment of postmenopausal osteoporosis: a network meta-analysis.Eur. Rev. Med. Pharmacol. Sci. 2019; 23: 2640-2668
- Efficacy of pharmacological therapies for the prevention of fractures in postmenopausal women: a network meta-snalysis.J. Clin. Endocrinol. Metab. 2019; 104: 1623-1630
Article info
Publication history
Published online: August 10, 2019
Accepted:
August 6,
2019
Received in revised form:
August 5,
2019
Received:
June 5,
2019
Identification
Copyright
© 2019 Elsevier B.V. All rights reserved.
