Current Controversies in Clinical Management of Postmenopausal Osteoporosis

 

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Abstract

Osteoporosis is a frequent disease in postmenopausal women. Despite the fact that fragility fractures cause many problems – a bio-psycho-social burden for the individual and an economic burden for the society – osteoporosis is still underdiagnosed and undertreated. Controversies exist concerning assessment with different tools for initiating a disease-specific treatment, patient monitoring with bone turnover markers, and treatment duration due to potential side effects in long-term treatment. This manuscript outlines and discusses these controversies and the presented cases, representatives for frequent clinical problems, may give guidance for the clinician in deciding how and how long to treat his/her patient. Re-evaluations of the patients on a regular basis are essential to warrant the necessity of treatment continuation and may improve patients’ compliance.

• References

• 1 Consensus development conference: prophylaxis and treatment of osteoporosis. Am J Med 1991; 90: 107-110
  CrossrefPubMedGoogle Scholar
• 2 Pietschmann P, Rauner M, Sipos W et al. Osteoporosis: An age-related and gender-specific disease – a mini-review. Gerontology 2009; 55: 3-12
  CrossrefPubMedGoogle Scholar
• 3 Kanis JA, Odén A, McCloskey EV et al. IOF Working Group on Epidemiology and Quality of Life. A systematic review of hip fracture incidence and probably of fracture worldwide. Osteoporos Int 2012; 23: 2239-2356
  CrossrefPubMedGoogle Scholar
• 4 Cooper C, Cole ZA, Holroyd CR et al. The IOF CSA Working Group on Fracture Epidemiology. Secular trends in the incidence of hip and other osteoporotic fractures. Osteoporos Int 2011; 22: 1277-1288
  Google Scholar
• 5 Dimai H-P, Svedbom A, Fahrleitner-Pammer A et al. Epidemiology of hip fractures in Austria: evidence for a change in the secular trend. Osteoporos Int 2011; 22: 685-692
  CrossrefPubMedGoogle Scholar
• 6 Van den Bergh JP, van Geel TA, Geusens PP. Osteoporosis, frailty and fracture: implications for case finding and therapy. Nature Reviews 2012; 8: 163-172
  PubMedGoogle Scholar
• 7 Kerschan-Schindl K, Patsch J, Kudlacek S et al. Measuring quality of life with the German Osteoporosis Quality of Life Questionnaire in women with osteoporosis. Wien Klin Wochenschr 2012; 124: 532-537
  CrossrefPubMedGoogle Scholar
• 8 Díez-Pérez A, Hooven FH, Adachi JD et al. Regional differences in treatment for osteoporosis. The Global Longitudinal Study of Osteoporosis in Women (GLOW). Bone 2011; 49: 493-498
  CrossrefPubMedGoogle Scholar
• 9 Pietschmann P, Azizi-Semrad U, Pils K et al. Pharmacologic undertreatment of osteoporosis in Austrian nursing homes and senior’s residences. Wien Klin Wochenschr 2010; 122: 532-537
  CrossrefPubMedGoogle Scholar
• 10 Reid IR. Overview of Pathogensis. In: Rosen CJ. editor-in-chief Primer on the metabolic bone diseases and disorders of mineral metabolism. 8^th edition John Wiley & Sons; 2013: 307-316
  CrossrefGoogle Scholar
• 11 Kanis JA, Melton III J, Christiansen C et al. Perspective The diagnosis of osteoporosis. J Bone Miner Res 1994; 9: 1137-1141
  PubMedGoogle Scholar
• 12 Bieglmayer C, Dimai HP, Gasser RW et al. Biomarkers of bone turnover in diagnosis and therapy of osteoporosis. Wien Med Wochenschr 2012; 162: 464-477
  CrossrefPubMedGoogle Scholar
• 13 Pietschmann P, Resch H, Woloszczuk W et al. A circadian rhythm of serum osteocalcin levels in postmenopausal osteoporosis. Eur J Clin Invest 1990; 20: 310-312
  PubMedGoogle Scholar
• 14 Netelenbos JC, Lems WF, Geusens PP et al. Spine radiographs to improve the identification of women at high risk for fractures. Osteoporos Int 2009; 20: 1347-1352
  CrossrefPubMedGoogle Scholar
• 15 Gallacher SJ, Gallagher AP, McQuillian C et al. The prevalence of vertebral fracture amongst patients presenting with non-vertebral fractures. Osteoporos Int 2007; 18: 185-192
  CrossrefPubMedGoogle Scholar
• 16 Helden van S, Geel van ACM, Geusens PP et al. Bone and fall-related fracture risks in women and men with a recent clinical fracture. J Bone Joint Surg Am 2008; 90: 241-248
  CrossrefPubMedGoogle Scholar
• 17 Kanis JA, Borgstrom F, de Laet C et al. Assessment of fracture risk. Osteoporos Int 2005; 16: 581-589
  CrossrefPubMedGoogle Scholar
• 18 Kanis JA, Oden A, Johnell O et al. The use of clinical risk factors enhances the performance of BMD in the prediction of hip and osteoporotic fractures in men and women. Osteoporos Int 2007; 18: 1033-1046
  CrossrefPubMedGoogle Scholar
• 19 Saag KG, Geusens P. Progress in osteoporosis and fracture prevention: focus on postmenopausal women. Arthritis Res Ther 2009; 11: 251 DOI: 10.1186/ar2815.
  CrossrefPubMedGoogle Scholar
• 20 Hippisley-Cox J, Coupland C. Predicting risk of osteoporotic fracture in men and women in England and Wales: prospective derivation and validation of QFractureScores. BMJ 2009; 339: b4229
  CrossrefPubMedGoogle Scholar
• 21 Hippisley-Cox J, Coupland C. Derivation and validation of updated QFracture algorithm to predict risk of osteoporotic fracture in primary care in the United Kingdom: prospective open cohort study. BMJ 2012; 344: e3427
  CrossrefPubMedGoogle Scholar
• 22 Nguyen ND, Frost SA, Center JA et al. Development of prognostic normograms for individualizing 5-year and 10-year fracture risks. Osteoporos Int 2008; 19: 1431-1444
  CrossrefPubMedGoogle Scholar
• 23 Bolland M, Siu ATY, Mason BH et al. Evaluation of the FRAX and Garvan Fracture risk calculators in older women. JBMR 2011; 26: 420-427
  CrossrefPubMedGoogle Scholar
• 24 Cummings NM, Poku EK, Towler MR et al. Clinical risk factors for osteoporosis in Ireland and the UK: a comparison of FRAX and QFractureScores. Calcif Tissue Int 2011; 89: 172-177
  CrossrefPubMedGoogle Scholar
• 25 Recker RR. Bone Biopsy and histomorphometry in clinical practice. In: Rosen CJ. editor-in-chief Primer on the metabolic bone diseases and disorders of mineral metabolism. 8^th edition. John Wiley & Sons; 2013: 307-316
  CrossrefGoogle Scholar
• 26 Roschger P, Paschalis EP, Fratzl P et al. Bone mineralization density distribution in health and disease. Bone 2008; 42: 456-466
  CrossrefPubMedGoogle Scholar
• 27 Bolland MJ, Grey A, Avenell A et al. Calcium supplements with or without vitamin D and risk of cardiovascular events: reanalysis of the Women’s Health Initiative limited access dataset and meta-analysis. BMJ 2011; 342: d2040
  CrossrefPubMedGoogle Scholar
• 28 Vogel VG, Costantino JP, Wickerham DL et al. National Surgical Adjuvant Breast and Bowel Project (NSABP). Effects of tamoxifen vs. raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial. JAMA 2006; 295: 2727-2741
  CrossrefPubMedGoogle Scholar
• 29 Seeman E. Raloxifene. Review article. JBMR 2001; 19: 65-75
  PubMedGoogle Scholar
• 30 Ettinger B, Black DM, Mitlak BH et al. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators. JAMA 1999; 282: 637-645
  CrossrefPubMedGoogle Scholar
• 31 Martino S, Cauley JA, Barett-Connor E et al. CORE Investigators. Continuing outcomes relevant to Evista: breast cancer incidence in postmenopausal osteoporotic women in a randomized trial of raloxifene. J Natl Cancer Inst 2004; 96: 1751-1761
  CrossrefPubMedGoogle Scholar
• 32 Cummings SR, Martin JS, Mc Clung MR et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. NEJM 2009; 361: 756-765
  CrossrefPubMedGoogle Scholar
• 33 Miller PD, Wagman RB, Peacock M et al. Effect of denosumab on bone mineral density and biochemical markers of bone turnover: 6 years results of a phase 2 clinical trial. JCEM 2011; 96: 394-402
  PubMedGoogle Scholar
• 34 Papapoulos S, Lippuner K, Roux C et al. Eight years of denosumab treatment in postmenopausal women with osteoporosis: results from the first five years of the FREEDOM extension. ASBMR 2013 Annual Meeting, Baltimore, Maryland
  PubMedGoogle Scholar
• 35 Neer R, Arnaud CD, Zanchettta JR et al. 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
  CrossrefPubMedGoogle Scholar
• 36 Meunier PJ, Roux C, Seeman E et al. The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. NEJM 2004; 350: 459-468
  CrossrefPubMedGoogle Scholar
• 37 Reginster JY, Kaufman JM, Goemaere S et al. Maintenance of antifracture efficacy over 10 years with strontium ranelate in postmenopausal osteoporosis. Osteoporos Int 2012; 23: 1115-1122
  CrossrefPubMedGoogle Scholar
• 38 Black DM, Thompson DE, Bauer DC et al. Fracture Intervention Trial. Fracture risk reduction with alendronate in women with osteoporosis: the Fracture Intervention Trial. J Clin Endocrinol Metab 2000; 85: 4118-4124
  CrossrefPubMedGoogle Scholar
• 39 Harris ST, Watts NB, Genant HK et al. Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis. JAMA 1999; 282: 1344-1352
  CrossrefPubMedGoogle Scholar
• 40 Eisman JA, Civitelli R, Adami S et al. Efficacy and tolerability of intravenous ibandronate injections in postmenopausal osteoporosis: 2-year results from the DIVA study. J Rheumatol 2008; 35: 488-497
  PubMedGoogle Scholar
• 41 Black DM, Delmas PD, Eastell R et al. HORIZON Pivotal Fracture Trial. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med 2007; 356: 1809-1822
  CrossrefPubMedGoogle Scholar
• 42 Roschger P, Rinnerthaler S, Yates J et al. Alendronate increases degree and uniformity of mineralization in cancellous bone and decreases the porosity in cortical bone of osteoporotic women. Bone 2001; 29: 185-191
  CrossrefPubMedGoogle Scholar
• 43 Zoehrer R, Roschger P, Fratzl P et al. Effects of 3- and 5-year treatment with Risedronate on the bone mineral density distribution of cancellous bone in human iliac crest biopsies. J Bone Miner Res 2006; 21: 1106-1112
  CrossrefPubMedGoogle Scholar
• 44 Boivin GY, Chavassieux PM, Santora AC et al. Alendronate increases bone strength by increasing the mean degree of mineralization of bone tissue in osteoporotic women. Bone 2000; 27: 687-964
  CrossrefPubMedGoogle Scholar
• 45 Borah B, Dufresne TE, Ritman EL et al. Long-term risedronate treatment normalizes mineralization and continues to preserve trabecular architecture: Sequential triple biopsy studies with micro-computed tomography. Bone 2006; 39: 345-352
  CrossrefPubMedGoogle Scholar
• 46 Misof BM, Roschger P, Gabriel D et al. Annual intravenous zoledronic acid for three years increased cancellous bone matrix mineralization beyond normal values in the HORIZON biopsy cohort. J Bone Miner Res 2013; 28: 442-448
  CrossrefPubMedGoogle Scholar
• 47 Black DM, Schwartz AV, Ensrud KE et al. FLEX Research Group . Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial. JAMA 2006; 296: 2927-2938
  CrossrefPubMedGoogle Scholar
• 48 Sorensen OH, Crawford GM, Mulder H et al. Longterm efficacy of risedronate: a 5 year placebo controlled clinical experience. Bone 2003; 32: 120-126
  CrossrefPubMedGoogle Scholar
• 49 Mellström DD, Sorensen OH, Goemaere S et al. Seven years of treatment with risedronate in women with postmenopausal osteoporosis. Calcif Tissue Int 2004; 75: 462-468
  CrossrefPubMedGoogle Scholar
• 50 Black DM, Reid IR, Boonen S et al. The effect of 3 versus 6 years of zoledronic acid treatment of osteoporosis: a randomized extension to the HORIZON – Pivotal Fracture Trial (PFT). J Bone Miner Res 2012; 27: 243-254
  CrossrefPubMedGoogle Scholar
• 51 Bianchi G, Czerwinski E, Kenwright A et al. Long-term administration of quarterly IV ibandronate is effective and well tolerated in postmenopausal osteoporosis: 5-year data from the DIVA study long-term extension. Osteoporos Int 2012; 23: 1769-1778
  CrossrefPubMedGoogle Scholar
• 52 Roschger P, Lombardi A, Misof BM et al. Mineralization density distribution of postmenopausal osteoporotic bone is restored to normal after long-term alendronate treatment: qBEI and sSAXS data from the fracture intervention trial long-term extension (FLEX). JBMR 2010; 25: 48-55
  CrossrefPubMedGoogle Scholar
• 53 Kerschan-Schindl K, Haschka J, Obermayer-Pietsch B et al. How long should women with postmenopausal osteoporosis be treated with a bisphosphonate?. Hormone Metabol Res 2013; 45: 621-628
  PubMedGoogle Scholar
• 54 Lo JC, O’Ryan FS, Gordon NP et al. Prevalence of osteonecrosis of the jaw in patients with oral bisphosphonate exposure. J Oral Maxillofac Surg 2010; 68: 243-253
  CrossrefPubMedGoogle Scholar
• 55 Cartsos VM, Zhu S, Zavras AI. Bisphosphonate use and the risk of adverse jaw outcomes. A medical claims study of 714217 people. J Am Dent Assoc 2008; 139: 23-30
  CrossrefPubMedGoogle Scholar
• 56 Shane E, Ebeling PR, Abrahamsen B et al. Atypical subtrochanteric and diaphyseal femoral fractures: Second report of a task force of the American society for bone and mineral research. JBMR 2014; 29: 1-23
  PubMedGoogle Scholar
• 57 Whitaker M, Guo J, Kehoe T et al. Bisphosphonates for osteoporosis – Where do we go from here?. N Engl J Med 2012; 366: 2048-2051
  CrossrefPubMedGoogle Scholar
• 58 Black DM, Bauer DC, Schwartz AV et al. Continuing bisphosphonate treatment for osteoporosis – for whom and for long?. N Engl J Med 2012; 366: 2051-2053
  CrossrefPubMedGoogle Scholar
• 59 Watts NB, Diab DL. Long-term use of bisphosphonates in osteoporosis. J Clin Endocrinol Metab 2010; 95: 1555-1565
  CrossrefPubMedGoogle Scholar
• 60 Ott S. What is the optimal duration of bisphosphonate therapy?. Cleveland Clinic Journal of Medicine 2011; 78: 619-630
  CrossrefPubMedGoogle Scholar
• 61 Eastell R, Walsh JS, Watts NB et al. Bisphosphonates for postmenopausal osteoporosis. Bone 2011; 49: 82-88
  CrossrefPubMedGoogle Scholar
• 62 Diab DL, Watts NB. Bisphosphonates in the treatment of osteoporosis. Endocrinol Metab Clin North Am 2012; 41: 487-506
  CrossrefPubMedGoogle Scholar
• 63 Boonen S, Ferrari S, Miller PD et al. Postmenopausal osteoporosis treatment with antiresorptives: effects of discontinuation or long-term continuation on bone turnover and fracture risk – a perspective. J Bone Miner Res 2012; 27: 963-974
  CrossrefPubMedGoogle Scholar
• 64 Briot K, Cortet B, Thomas T et al. 2012 update of French guidelines for the pharmacological treatment of postmenopausal osteoporosis. J Bone Spine 2012; 79: 304-313
  CrossrefPubMedGoogle Scholar
• 65 Lindsay R, Scheele WH, Neer R et al. Sustained vertebral fracture risk reduction after withdrawal of teriparatide in postmenopausal women with osteoporosis. Arch Int Med 2004; 164: 2024-2030
  CrossrefPubMedGoogle Scholar
• 66 Prince R, Spipos A, Hossain A et al. Sustained non-vertebral fragility fracture risk reduction after discontinuation of teriparatide treatment. J Bone Miner Res 2005; 20: 1507-1513
  CrossrefPubMedGoogle Scholar
• 67 Watts NB, Diab DL. Long-term use of bisphosphonates in osteoporosis. J Clin Endocrinol Metab 2010; 95: 1555-1565
  CrossrefPubMedGoogle Scholar
• 68 Bagger YZ, Tankó LB, Alexandersen P et al. Alendronate has a residual effect on bone mass in postmenopausal Danish women up to 7 years after treatment withdrawal. Bone 2003; 33: 301-307
  CrossrefPubMedGoogle Scholar