658
Views
19
CrossRef citations to date
0
Altmetric
Review

New and developing pharmacotherapy for osteoporosis in men

&
Pages 253-264 | Received 18 Aug 2017, Accepted 12 Jan 2018, Published online: 19 Jan 2018

References

  • Gennari L, Bilezikian JP. Osteoporosis in men. Endocrinol Metab Clin N Am. 2007;36:399–419.
  • Melton LJ. Epidemiology of fractures. In: Riggs BL, Melton LJ, editors. Osteoporosis: etiology, diagnosis and management. Second ed. Philadelphia: Lippincott-Raven Publishers; 1995. p. 225–247.
  • Gullberg B, Johnell O, Kanis JA. World-wide projections for hip fracture. Osteoporos Int. 1997;7:407–413.
  • Center JR, Nguyen TV, Schneider D, et al. Mortality after all major types of osteoporotic fracture in men and women: an observational study. Lancet. 1999;353:878–882.
  • Haentjens P, Magaziner J, Colón-Emeric CS, et al. Meta-analysis: excess mortality after hip fracture among older women and men. Ann Intern Med. 2010;152:380–390.
  • Bliuc D, Nguyen ND, Milch VE, et al. Mortality risk associated with low-trauma osteoporotic fracture and subsequent fracture in men and women. JAMA. 2009;301:513–521.
  • Jiang HX, Majumdar SR, Dick DA, et al. Development and initial validation of a risk score for predicting in-hospital and 1-year mortality in patients with hip fractures. J Bone Miner Res. 2005;20:494–500.
  • Schurch MA, Rizzoli R, Mermillod B, et al. A prospective study on socioeconomic aspects of fracture of the proximal femur. J Bone Miner Res. 1996;11:1935–1942.
  • Johnell O, Kanis JA. An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int. 2006;17:1726–1733.
  • Burge R, Dawson-Hughes B, Solomon DH, et al. Incidence and economic burden of osteoporosis-related fractures in the United States. J Bone Miner Res. 2007;22:465–475.
  • Center JR, Bliuc D, Nguyen ND, et al. Risk of subsequent fracture after low-trauma fracture in men and women. JAMA. 2007;297:387–394.
  • Khosla S, Amin S, Orwoll E. Osteoporosis in men. Endocr Rev. 2008;29:441–464.
  • Gennari L, Bilezikian JP. Idiopathic osteoporosis in men. Curr Osteoporos Rep. 2013;11:286–l98.
  • Mackey DC, Lui LY, Cawthon PM, et al. Study of osteoporotic fractures (SOF) and osteoporotic fractures in men (MrOS) research groups. High-trauma fractures and low bone mineral density in older women and men. JAMA. 2007;298:2381–2388.
  • Amin S, Melton LJ III, Achenbach SJ, et al. A distal forearm fracture in childhood is associated with an increased risk for future fragility fractures in adult men, but not women. J Bone Miner Res. 2013;28:1751–1759.
  • Ensrud KE, Taylor BC, Peters KW, et al. Osteoporotic fractures in men study group. Implications of expanding indications for drug treatment to prevent fracture in older men in United States: cross sectional and longitudinal analysis of prospective cohort study. Bmj. 2014;349:g4120.
  • Cosman F, de Beur SJ, LeBoff MS, et al. Clinician’s guide to prevention and treatment of osteoporosis. Osteoporos Int. 2014;25:2359–2381. Erratum in: Osteoporos Int 2015;26:2045-7
  • Duan Y, Beck TJ, Wang X-F, et al. Structural and biomechanical basis of sexual dimorphism in femoral neck fragility has its origins in growth and aging. J Bone Miner Res. 2003;18:1766–1774.
  • Wang XF, Duan Y, Beck T, et al. Varying contributions of growth and ageing to racial and sex differences in femoral neck structure and strength in old age. Bone. 2005;36:978–986.
  • Seeman E. Osteoporosis in men: epidemiology, pathophysiology, and treatment possibilities. Am J Med. 1993;95(Suppl5A):22–28.
  • Napoli N, Chandran M, Pierroz DD, et al. IOF bone and diabetes working group. Mechanisms of diabetes mellitus-induced bone fragility. Nat Rev Endocrinol. 2017;13:208–219.
  • Gennari L, Klein R, Ferrari S. The genetics of peak bone mass. In: Orwoll E, Bilezikian JP, Vanderschueren D, editors. Osteoporosis in men. 2nd ed. Section 3. Skeletal Genetics. London, UK: Academic Press; 2009.
  • Van Pottelbergh I, Goemaere S, Zmierczak H, et al. Deficient acquisition of bone during maturation underlies idiopathic osteoporosis in men: evidence from a three generation family study. J Bone Miner Res. 2003;18:303–311.
  • Lara-Castillo N, Johnson ML. LRP receptor family member associated bone disease. Rev Endocr Metab Disord. 2015;16:141–148.
  • Szulc P, Joly-Pharaboz MO, Marchand F, et al. Insulin-like growth factor I is a determinant of hip bone mineral density in men less than 60 years of age: MINOS study. Calcif Tissue Int. 2004;74:322–329.
  • Rosen CJ, Kurland ES, Vereault D, et al. An association between serum IGF-1 and a simple sequence repeat in the IGF-1 gene: implications for genetic studies of bone mineral density. J Clin Endocrinol Metab. 1998;83:2286–2290.
  • Lorentzon M, Swanson C, Andersson N, et al. Free testosterone is a positive, whereas free estradiol is a negative, predictor of cortical bone size in young Swedish men: the GOOD study. J Bone Miner Res. 2005;20:1334–1341.
  • Kaufman JM, Vermeulen A. Declining gonadal function in elderly men. Baillieres Clin Endocrinol Metab. 1997;11:289–309.
  • Riggs BL, Khosla S, Melton LJ 3rd. Sex steroids and the construction and conservation of the adult skeleton. Endocr Rev. 2002;23:279–302.
  • Khosla S, Oursler MJ, Monroe DG. Estrogen and the skeleton. Trends Endocrinol Metab. 2012;23:576–581.
  • Gennari L, Nuti R, Bilezikian JP. Aromatase activity and bone homeostasis in men. J Clin Endocrinol Metab. 2004;89:5898–5907.
  • Khosla S, Melton LJ III, Atkinson EJ, et al. Relationship of serum sex steroid levels to longitudinal changes in bone density in young vs elderly men. J Clin Endocrinol Metab. 2001;86:3555–3561.
  • Gennari L, Merlotti D, Martini G, et al. Longitudinal association between sex hormone levels, bone loss, and bone turnover in elderly men. J Clin Endocrinol Metab. 2003;88:5327–5333.
  • Cummings SR, Cawthon PM, Ensrud KE, et al. Osteoporotic fractures in men (MrOS) research groups; Study of osteoporotic fractures research groups. BMD and risk of hip and nonvertebral fractures in older men: a prospective study and comparison with older women. J Bone Miner Res. 2006;21:1550–1556.
  • Watts NB, Adler RA, Bilezikian JP, et al. Endocrine society. Osteoporosis in men: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2012;97:1802–1822.
  • Lewiecki EM, Baim S, Langman CB, et al. The official positions of the International Society for Clinical Densitometry: perceptions and commentary. J Clin Densitom. 2009;12:267–271.
  • Kaufman JM, Reginster JY, Boonen S, et al. Treatment of osteoporosis in men. Bone. 2013;53:134–144.
  • Schousboe JT, Vokes T, Broy SB, et al. Vertebral fracture assessment: the 2007 ISCD official positions. J Clin Densitom. 2008;11:92–108.
  • Szulc P. Biochemical bone turnover markers and osteoporosis in older men: where are we? J Osteoporos. 2011;2011:704015.
  • Bauer DC, Garnero P, Harrison SL, et al. Biochemical markers of bone turnover, hip bone loss, and fracture in older men: the MrOS study. J Bone Miner Res. 2009;24:2032–2038.
  • Tosteson AN, Melton LJ III, Dawson-Hughes B, et al. National osteoporosis foundation guide committee. Cost-effective osteoporosis treatment thresholds: the United States perspective. Osteoporos Int. 2008;19:437–447.
  • Buckley L, Guyatt G, Fink HA, et al. American college of rheumatology guideline for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Care Res (Hoboken). 2017;69:1095–1110.
  • Fraser LA, Langsetmo L, Berger C, et al. CaMos Research Group. Fracture prediction and calibration of a Canadian FRAX tool: a population-based report from CaMos. Osteoporos Int. 2011;22:829–837.
  • Ettinger B, Ensrud KE, Blackwell T, et al. Performance of FRAX in a cohort of community-dwelling, ambulatory oldermen: the osteoporotic fractures in men (MrOS) study. Osteoporos Int. 2013;24:1185–1193.
  • Kanis JA, Bianchi G, Bilezikian JP, et al. Towards a diagnostic and therapeutic consensus in male osteoporosis. Osteoporos Int. 2011;22:2789–2798.
  • Orimo H, Nakamura T, Hosoi T, et al. Japanese 2011 guidelines for prevention and treatment of osteoporosis–executive summary. Arch Osteoporos. 2012;7:3–20.
  • Blain H, Masud T, Dargent-Molina P, et al. EUGMS Falls and Fracture Interest Group; International Association of Gerontology and Geriatrics for the European Region (IAGG-ER); European Union of Medical Specialists (EUMS); Fragility Fracture Network (FFN); European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO); and International Osteoporosis Foundation (IOF). A comprehensive fracture prevention strategy in older adults: the European Union Geriatric Medicine Society (EUGMS) statement. Aging Clin Exp Res. 2016;28:797–803.
  • Reginster JY, Abadie E, Delmas P, et al. Recommendations for an update of the current (2001) regulatory requirements for registration of drugs to be used in the treatment of osteoporosis in postmenopausal women and in men. Osteoporos Int. 2006;17:1–7.
  • Murad MH, Mullan R, Drake M, et al. Comparative effectiveness of drug treatments to prevent fragility fractures: a systematic review and network meta-analysis. J Clin Endocrinol Metab. 2012;97:1861–1870.
  • Orwoll E, Ettinger M, Weiss S, et al. Alendronate for the treatment of osteoporosis in men. N Engl J Med. 2000;343:604–610.
  • Gonnelli S, Cepollaro C, Montagnani A, et al. Alendronate treatment in men with primary osteoporosis: a three-year longitudinal study. Calcif Tissue Int. 2003;73:133–139.
  • Miller PD, Schnitzer T, Emkey R, et al. Weekly oral alendronic acid in male osteoporosis. Clin Drug Investig. 2004;24:333–341.
  • Boonen S, Lorenc RS, Wenderoth D, et al. Evidence for safety and efficacy of risedronate in men with osteoporosis over 4 years of treatment: results from the 2-year, open-label, extension study of a 2-year, randomized, double-blind, placebo-controlled study. Bone. 2012;51:383–388.
  • Boonen S, Orwoll ES, Wenderoth D, et al. Once-weekly risedronate in men with osteoporosis: results of a 2-year, placebo-controlled, double-blind, multicenter study. J Bone Miner Res. 2009;24:719–725.
  • Sawka AM, Papaioannou A, Adachi JD, et al. Does alendronate reduce the risk of fracture in men? A meta-analysis incorporating prior knowledge of anti-fracture efficacy in women. BMC Musculoskelet Disord. 2005;6:39.
  • Ringe JD, Farahmand P, Faber H, et al. Sustained efficacy of risedronate in men with primary and secondary osteoporosis: results of a 2-year study. Rheumatol Int. 2009;29:311–315.
  • Sato Y, Iwamoto J, Kanoko T, et al. Risedronate sodium therapy for prevention of hip fracture in men 65 years or older after stroke. Arch Int Med. 2005;165:1743–1748.
  • Boonen S, Reginster JY, Kaufman JM, et al. Fracture risk and zoledronic acid therapy in men with osteoporosis. N Engl J Med. 2012;367:1714–1723.
  • Lyles KW, Colón-Emeric CS, HORIZON Recurrent Fracture Trial, et al.; Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med. 2007;357:1799–1809.
  • Boonen S, Orwoll E, HORIZON Recurrent Fracture Trial, et al.; Once-yearly zoledronic acid in older men compared with women with recent hip fracture. J Am Geriatr Soc. 2011;59:2084–2090.
  • Smith MR, Egerdie B, Denosumab HALT Prostate Cancer Study Group, et al. Denosumab in men receiving androgen-deprivation therapy for prostate cancer. N Engl J Med. 2009;361:745–755.
  • Smith MR, Saad F, Coleman R, et al. Denosumab and bone‑metastasis‑free survival in men with castration-resistant prostate cancer: results of a phase 3, randomised, placebo-controlled trial. Lancet. 2012;379:39–46.
  • Orwoll E, Teglbjærg CS, Langdahl BL, et al. A randomized, placebo-controlled study of the effects of denosumab for the treatment of men with low bone mineral density. J Clin Endocrinol Metab. 2012;97:3161–3169.
  • Slovik DM, Rosenthal DI, Doppelt SH, et al. Restoration of spinal bone in osteoporotic men by treatment with human parathyroid hormone (1–34) and 1,25- dihydroxyvitamin D. J Bone Miner Res. 1986;1:377–381.
  • Kurland ES, Cosman F, McMahon DJ, et al. Parathyroid hormone as a therapy for idiopathic osteoporosis in men: effects on bone mineral density and bone markers. J Clin Endocrinol Metab. 2000;85:3069–3076.
  • Orwoll ES, Scheele WH, Paul S, et al. The effect of teriparatide [human parathyroid hormone (1–34)] therapy on bone density in men with osteoporosis. J Bone Miner Res. 2003;18:9–17.
  • 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. N Engl J Med. 2001;344:1434–1441.
  • Kaufman JM, Orwoll E, Goemaere S, et al. Teriparatide effects on vertebral fractures and bone mineral density in men with osteoporosis: treatment and discontinuation of therapy. Osteoporos Int. 2005;16:510–516.
  • Saag KG, Shane E, Boonen S, et al. Teriparatide or alendronate in glucocorticoid-induced osteoporosis. N Engl J Med. 2007;357:2028–2039.
  • Saag KG, Zanchetta JR, Devogelaer JP, et al. Effects of teriparatide vs alendronate for treating glucocorticoid-induced osteoporosis: 36- month results of a randomized, double-blind, controlled trial. Arthritis Rheum. 2009;60:3346–3355.
  • Canalis E, Giustina A, Bilezikian JP. Mechanisms of anabolic therapies for osteoporosis. N Engl J Med. 2007;357:905–916.
  • Finkelstein JS, Hayes A, Hunzelman JL, et al. The effects of parathyroid hormone, alendronate, or both in men with osteoporosis. N Engl J Med. 2003;349:1216–1226.
  • Walker MD, Cusano NE, Sliney J Jr, et al. Combination therapy with risedronate and teriparatide in male osteoporosis. Endocrine. 2013;44:237–246.
  • Bilezikian JP, Rubin MR. Combination/sequential therapies for anabolic and antiresorptive skeletal agents for osteoporosis. Curr Osteoporos Rep. 2006;4:5–13.
  • Meunier PJ, Roux C, Seeman E, et al. The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. N Engl J Med. 2004;350:459–468.
  • Reginster JY, Seeman E, De Vernejoul MC, et al. Strontium ranelate reduces the risk of non vertebral fractures in postmenopausal women with osteoporosis: treatment of peripheral osteoporosis (TROPOS) study. J Clin Endocrinol Metab. 2005;90:2816–2822.
  • Kaufman JM, Audran M, Bianchi G, et al. Efficacy and safety of strontium ranelate in the treatment of osteoporosis in men. J Clin Endocrinol Metab. 2013;98:592–601.
  • Anderson FH, Francis RM, Peaston RT, et al. Androgen supplementation in eugonadal men with osteoporosis: effects of 6 month’s treatment on markers of bone formation and resorption. J Bone Miner Res. 1997;12:472–478.
  • Tracz MJ, Sideras K, Bolona ER, et al. Testosterone use in men and its effects on bone health. A systematic review and meta-analysis of randomized placebo controlled trials. J Clin Endocrinol Metab. 2006;91:2011–2016.
  • Basaria S, Coviello AD, Travison TG, et al. Adverse events associated with testosterone administration. N Engl J Med. 2010;363:109–122.
  • Gennari L, Rotatori S, Bianciardi S, et al. Appropriate models for novel osteoporosis drug discovery and future perspectives. Expert Opin Drug Discov. 2015;10:1201–1216.
  • Gennari L, Rotatori S, Bianciardi S, et al. Treatment needs and current options for postmenopausal osteoporosis. Expert Opin Pharmacother. 2016;17:1141–1152.
  • Costa AG, Cusano NE, Silva BC, et al. Cathepsin K: its skeletal actions and role as a therapeutic target in osteoporosis. Nat Rev Rheumatol. 2011;7:447–456.
  • Langdahl B, Binkley N, Bone H, et al. Odanacatib in the treatment of postmenopausal women with low bone mineral density: five years of continued therapy in a phase 2 study. J Bone Miner Res. 2012;27:2251–2258.
  • Eisman JA, Bone HG, Hosking DJ, et al. Odanacatib in the treatment of postmenopausal women with low bone mineral density: three-year continued therapy and resolution of effect. J Bone Miner Res. 2011;26:242–251.
  • Bone HG, Dempster DW, Eisman JA, et al. Odanacatib for the treatment of postmenopausal osteoporosis: development history and design and participant characteristics of LOFT, the long-term odanacatib fracture trial. Osteoporos Int. 2015;26:699–712.
  • Mullard A. Merck &Co. Drops osteoporosis drug odanacatib. Nat Rev Drug Discov. 2016;15:669.
  • Drake MT, Clarke BL, Oursler MJ, et al. Cathepsin K inhibitors for osteoporosis: biology, potential clinical utility, and lessons learned. Endocr Rev. 2017;38:325–350.
  • Kartner N, Manolson MF. Novel techniques in the development of osteoporosis drug therapy: the osteoclast ruffled-border vacuolar H (+)-ATPase as an emerging target. Expert Opin Drug Discov. 2014;9:505–522.
  • Okazaki M, Potts JT, Gardella TJ. Identification and optimization of residues in PTH and PTHrP that determine altered modes of binding to the PTH/PTHrP receptor. J Bone Miner Res. 2008;23:S103.
  • Dean T, Vilardaga JP, Potts JT Jr, et al. Altered selectivity of parathyroid hormone (PTH) and PTH-related protein (PTHrP) for distinct conformations of the PTH/PTHrP receptor. Mol Endocrinol. 2008;22:156e66.
  • Cosman F. Abaloparatide: a new anabolic therapy on the horizon. Bonekey Rep. 2015;4:661.
  • Hattersley G, Dean T, Corbin BA, et al. Binding selectivity of abaloparatide for PTH-Type-1-receptor conformations and effects on downstream signaling. Endocrinology. 2016;157:141–149.
  • Leder BZ, O’Dea LS, Zanchetta JR, et al. 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.
  • Miller PD, Hattersley G, Riis BJ, et al. ACTIVE study investigators. Effect of abaloparatide vs placebo on new vertebral fractures in postmenopausal women with osteoporosis: a randomized clinical trial. JAMA. 2016;316:722–733.
  • Cosman F, Miller PD, Williams GC, et al. Eighteen months of treatment with subcutaneous abaloparatide followed by 6 months of treatment with alendronate in postmenopausal women with osteoporosis: results of the ACTIVExtend trial. Mayo Clin Proc. 2017;92:200–210.
  • Baron R, Rawadi G. Wnt signaling and the regulation of bone mass. Curr Osteoporos Rep. 2007;5:73–80.
  • Manolagas SC. Wnt signaling and osteoporosis. Maturitas. 2014;78:233–237.
  • Papapoulos SE. Targeting sclerostin as potential treatment of osteoporosis. Ann Rheum Dis. 2011;70:i119–i122.
  • van Lierop AH, Hamdy NA, Hamersma H, et al. Patients with sclerosteosis and disease carriers: human models of the effect of sclerostin on bone turnover. J Bone Min Res. 2011;26:2804–2811.
  • Das S, Sakthiswary R. Bone metabolism and histomorphometric changes in murine models treated with sclerostin antibody: a systematic review. Curr Drug Targets. 2013;14:1667–1674.
  • McClung MR, Grauer A, Boonen S, et al. Romosozumab in postmenopausal women with low bone mineral density. N Engl J Med. 2014;370:412–420.
  • Cosman F, Crittenden DB, Adachi JD, et al. Romosozumab treatment in postmenopausal women with osteoporosis. N Engl J Med. 2016;375:1532–1543.
  • [cited 2017 Jul 25]. Available from: http://www.amgen.pt/media/media_pr_detail.jsp?year=&releaseID=2275391
  • Feurer E, Chapurlat R. Emerging drugs for osteoporosis. Expert Opin Emerging Drugs. 2014;19:1–11.
  • Gillberg P, Mallmin H, Petrén-Mallmin M, et al. Two years of treatment with recombinant human growth hormone increases bone mineral density in men with idiopathic osteoporosis. J Clin Endocrinol Metab. 2002;87:4900–4906.
  • Smith MR, Fallon MA, Lee H, et al. Raloxifene to prevent gonadotropin-releasing hormone agonist-induced bone loss in men with prostate cancer: a randomized controlled trial. J Clin Endocrinol Metab. 2004;89:3841–3846.
  • Smith MR, Morton RA, Barnette KG, et al. Toremifene to reduce fracture risk in men receiving androgen deprivation therapy for prostate cancer. J Urol. 2013;189(1Suppl):S45–50.
  • Doran PM, Riggs BL, Atkinson EJ, et al. Effects of raloxifene, a selective estrogen receptor modulator, on bone turnover markers and serum sex steroid and lipid levels in elderly men. J Bone Miner Res. 2001;16:2118–2125.
  • Uebelhart B, Herrmann F, Pavo I, et al. Raloxifene treatment is associated with increased serum estradiol and decreased bone remodeling in healthy middle-aged men with low sex hormone levels. J Bone Miner Res. 2004;19:1518–1524.
  • Dalton JT, Mukherjee A, Zhu Z, et al. Discovery of nonsteroidal androgens. Biochem Biophys Res Commun. 1998;244:1e4.
  • Clarke BL, Khosla S. Modulators of androgen and estrogen receptor activity. Crit Rev Eukaryot Gene Expr. 2010;20:275–294.
  • Narayanan R, Coss CC, Dalton JT. Development of selective androgen receptor modulators (SARMs). Mol Cell Endocrinol. 2017;pii: S0303-7207(17)30340-4. doi:10.1016/j.mce.2017.06.013. [Epub ahead of print]
  • Schwartz AV, Pavo I, Alam J, et al. Teriparatide in patients with osteoporosis and type 2 diabetes. Bone. 2016;91:152–158.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.