a repository copy of Pharmacologic intervention for prevention of fractures in osteopenic and osteoporotic postmenopausal women: Systemic review and meta-analysis

Objectives: Emerging evidence has indicated a role for pharmacologic agents in the primary prevention of osteoporotic fracture, but have not yet been systematically reviewed for meta-analysis. We conducted a meta-analysis to evaluate the eficacy of pharmacologic interventions in reducing fracture risk and increasing bone mineral density (BMD) in postmenopausal women with osteopenia or osteoporosis but without prevalent fragility fracture. Method: The Medline, EMBASE, and CENTRAL databases were searched from inception to September 30, 2019. Only randomized placebo-controlled trials evaluating postmenopausal women with − 1.0 > bone mineral density (BMD) T-score > − 2.5 (low bone mass) and those with BMD T-score ≤ − 2.5 (osteoporosis) but without baseline fractures, who were receiving anti-osteoporotic agents, providing quantitative outcomes data and evaluating risk of vertebral and/or non-vertebral fragility fracture at follow-up. The PRISMA guidelines were followed, applying a random-effects model. The primary endpoint was the effect of anti-osteoporotic regimens in reducing the incidence of vertebral fractures. Secondary endpoints were percentage changes in baseline BMD at the lumbar spine and total hip at 1 and 2 years follow up. Results: Full-text review of 144 articles yielded, 20 for meta-analysis. Bisphosphonates reduced the risk of vertebral fracture (pooled OR = 0.50, 95%CIs = 0.36 – 0.71) and signiicantly increased lumbar spine BMD after 1 year, by 4.42% vs placebo (95%CIs = 3.70% – 5.14%). At the hip, this value was 2.94% (95%CIs = 2.13% – 3.75%). Overall results of limited studies for non-bisphosphonate drugs showed increased BMD and raloxifene signiicantly decreases the risk of subsequent clinical vertebral fractures. Conclusion: The bisphosphonates are eficacious and most evident for the primary prevention of osteoporotic vertebral fractures, reducing their incidence and improving BMD in postmenopausal women with osteopenia or osteoporosis.

[1]  Iqra Qamar,et al.  Role of Bisphosphonate Therapy in Patients with Osteopenia: A Systemic Review , 2019, Cureus.

[2]  J. Cauley,et al.  Change in Bone Density and Reduction in Fracture Risk: A Meta‐Regression of Published Trials , 2019, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[3]  D. Solomon,et al.  Comparison of Denosumab and Bisphosphonates in Patients With Osteoporosis: A Meta-Analysis of Randomized Controlled Trials. , 2018, The Journal of clinical endocrinology and metabolism.

[4]  I. Reid,et al.  Fracture Prevention with Zoledronate in Older Women with Osteopenia , 2018, The New England journal of medicine.

[5]  Qingsheng Zhang,et al.  Denosumab compared to bisphosphonates to treat postmenopausal osteoporosis: a meta-analysis , 2018, Journal of Orthopaedic Surgery and Research.

[6]  M. Phipps,et al.  Screening for Osteoporosis to Prevent Fractures: US Preventive Services Task Force Recommendation Statement , 2018, JAMA.

[7]  A. Grauer,et al.  Romosozumab increases bone mineral density in postmenopausal Japanese women with osteoporosis: A phase 2 study. , 2017, Bone.

[8]  I. Reid,et al.  Duration of antiresorptive activity of zoledronate in postmenopausal women with osteopenia: a randomized, controlled multidose trial , 2017, Canadian Medical Association Journal.

[9]  A. Qaseem,et al.  Treatment of Low Bone Density or Osteoporosis to Prevent Fractures in Men and Women: A Clinical Practice Guideline Update From the American College of Physicians. , 2017, Annals of internal medicine.

[10]  L. Sànchez-Riera,et al.  Fragility Fractures & Their Impact on Older People. , 2017, Best practice & research. Clinical rheumatology.

[11]  V. Gudnason,et al.  Imminent risk of fracture after fracture , 2017, Osteoporosis International.

[12]  Yu-sheng Li,et al.  Network Meta-Analysis of Pharmacological Agents for Osteoporosis Treatment and Fracture Prevention , 2016, Cellular Physiology and Biochemistry.

[13]  R. Eastell,et al.  Response of bone turnover markers to raloxifene treatment in postmenopausal women with osteopenia , 2016, Osteoporosis International.

[14]  J. Shen,et al.  Influences of teriparatide administration on marrow fat content in postmenopausal osteopenic women using MR spectroscopy , 2016, Climacteric : the journal of the International Menopause Society.

[15]  Dongbao Zhao,et al.  Indirect comparison of teriparatide, denosumab, and oral bisphosphonates for the prevention of vertebral and nonvertebral fractures in postmenopausal women with osteoporosis , 2015, Menopause.

[16]  Cesar Libanati,et al.  Romosozumab in postmenopausal women with low bone mineral density , 2014, The New England journal of medicine.

[17]  I. Reid,et al.  Duration of Antiresorptive Effects of Low‐Dose Zoledronate in Osteopenic Postmenopausal Women: A Randomized, Placebo‐Controlled Trial , 2014, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[18]  E. Vittinghoff,et al.  BMD changes and predictors of increased bone loss in postmenopausal women after a 5‐year course of alendronate , 2013, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[19]  J. Sterne,et al.  The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials , 2011, BMJ : British Medical Journal.

[20]  J. Ioannidis,et al.  Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials , 2011, BMJ : British Medical Journal.

[21]  E. Eriksen Treatment of osteopenia , 2011, Reviews in Endocrine and Metabolic Disorders.

[22]  E. Siris,et al.  Primary Care Use of FRAX®: Absolute Fracture Risk Assessment in Postmenopausal Women and Older Men , 2010, Postgraduate medicine.

[23]  C. Benhamou,et al.  Zoledronic Acid for the Prevention of Bone Loss in Postmenopausal Women With Low Bone Mass: A Randomized Controlled Trial , 2009, Obstetrics and gynecology.

[24]  I. Reid,et al.  The antiresorptive effects of a single dose of zoledronate persist for two years: a randomized, placebo-controlled trial in osteopenic postmenopausal women. , 2009, The Journal of clinical endocrinology and metabolism.

[25]  J. S. San Martin,et al.  Effects of denosumab on bone mineral density and bone turnover in postmenopausal women. , 2008, The Journal of clinical endocrinology and metabolism.

[26]  A. Grauer,et al.  Effects of risedronate on fracture risk in postmenopausal women with osteopenia , 2007, Osteoporosis International.

[27]  S. Jamal,et al.  Low bone mineral density and fracture burden in postmenopausal women , 2007, Canadian Medical Association Journal.

[28]  P. Miller,et al.  Denosumab in Postmenopausal Women with Low Bone Mineral Density , 2007 .

[29]  M. Nevitt,et al.  Effect of alendronate on vertebral fracture risk in women with bone mineral density T scores of-1.6 to -2.5 at the femoral neck: the Fracture Intervention Trial. , 2005, Mayo Clinic proceedings.

[30]  O. Johnell,et al.  Effect of raloxifene on the risk of new vertebral fracture in postmenopausal women with osteopenia or osteoporosis: a reanalysis of the Multiple Outcomes of Raloxifene Evaluation trial. , 2003, Bone.

[31]  B. Stuckey,et al.  Alendronate prevents loss of bone density associated with discontinuation of hormone replacement therapy: a randomized controlled trial. , 2003, Archives of internal medicine.

[32]  Jacques P. Brown,et al.  Intravenous zoledronic acid in postmenopausal women with low bone mineral density. , 2002, The New England journal of medicine.

[33]  P Geusens,et al.  Risk of new vertebral fracture in the year following a fracture. , 2001, JAMA.

[34]  M. Yen,et al.  Effects of alendronate on osteopenic postmenopausal Chinese women. , 2000, Bone.

[35]  B. Walsh,et al.  Comparison of alendronate and intranasal calcitonin for treatment of osteoporosis in postmenopausal women. , 2000, The Journal of clinical endocrinology and metabolism.

[36]  A. LaCroix,et al.  Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial. , 1998, JAMA.

[37]  A. Phillips The Fracture Intervention Trial , 1997, The Lancet.

[38]  N. Ghannam,et al.  Book review: Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. , 1994, Annals of Saudi medicine.

[39]  D. Felsenberg,et al.  Impact of oral ibandronate 150 mg once monthly on bone structure and density in post-menopausal osteoporosis or osteopenia derived from in vivo μCT. , 2012, Bone.

[40]  C. Christiansen,et al.  The effect on bone mass and bone markers of different doses of ibandronate — A new bisphosphonate for prevention and treatment of postmenopausal osteoporosis. A 1-year, randomized, double-blind, placebo-controlled dose-finding study , 2006, Osteoporosis International.

[41]  Claus Christiansen,et al.  Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Report of a WHO Study Group. , 1994, World Health Organization technical report series.