Therapeutic options in male osteoporosis

Summary

Osteoporosis in men is increasingly recognized as an important public health problem but affected patients are still under-diagnosed and -treated. As in women the diagnostic and therapeutic strategy has to be adapted to the individual case. In the practical management it is very important to detect possible causes of secondary osteoporosis, to explain the possibilities of basic therapy counteracting individual risk factors and communicate that osteoporosis is a chronic disease and adherence to a long-term treatment is crucial. In established severe osteoporosis a careful analgesic therapy is important to avoid further bone loss related to immobility. In elderly men with increased risk of falling insufficient Vitamin D supply or impaired activation of Vitamin D due to renal insufficiency must be taken into consideration. Specific medications available today for the treatment of male osteoporosis comprise among antiresorptive drugs the bis phosphonates alendronate, risedronate and zoledronic acid. Denosumab, the first biological therapy is approved for men with androgen deprivation therapy for prostate cancer. An important advantage of this potent antiresorptive drug is the increased adherence due to the comfortable application by sixmonthly subcutaneous injections. Study results from the 2-year multi-center randomized controlled ADAMO-Study will very soon allow the use of denosumab in all types of male osteoporosis. Teriparatide, the 34 N-terminal amino acid sequence of parathyroid hormone was approved for men with osteoporosis as an anabolic agent based on proven efficacy by different studies. Among drugs with other modes of action the D-hormone pro-drug alfacalcidol can be used in men alone or in combination with the advantage of pleiotropic effects on calcium absorption, parathyroids, bone and muscle. Recently also Strontium-ranelate was approved for male patients with the limitation to exclude men with clinical relevant cardiovascular risk factors. In general the possibilities to treat male osteoporosis have considerably improved during recent years. Today there is a choice of a spectrum of drugs from mild to strong potency with different modes of action on bone turnover to design strategies for individual male patients.

Zusammenfassung

Obwohl die Osteoporose des Mannes zunehmend als relevantes Gesundheitsproblem anerkannt wird, werden die Betroffenen immer noch zu selten diagnostiziert und oft ungenügend therapiert. Wie bei Frauen muss sich das diagnostische und therapeutische Vorgehen den Problemen des Einzelfalles anpassen. Bei der praktischen Patientenbetreuung ist es sehr wichtig, eventuelle Ursachen sekundärer Osteoporosen aufzudecken, die Möglichkeiten der Basistherapie, die individuellen Risikofaktoren entgegenwirken können, genau zu erklären und dem Patienten klar zu machen, dass die Diagnose Osteoporose eine chronische Erkrankung bedeutet und damit die Therapietreue über viele Jahre ganz entscheidend ist. Bei manifester Osteoporose ist eine sorgfältige Schmerztherapie sehr wichtig, um immobilitätsbedingten weiteren Knochenverlust zu vermeiden. Bei älteren Männern mit erhöhtem Sturzrisiko muss ungenügende Vitamin-D-Zufuhr oder gehemmte Aktivierung infolge einer Niereninsuffizienz in Betracht gezogen werden. Die heute verfügbaren spezifischen Medikamente zur Therapie der männlichen Osteoporose umfassen unter den antiresorptiven Medikamenten die Bisphosphonate Alendronat, Risedronat und Zoledronsäure. Denosumab, die erste biologische Therapie der Osteoporose, wurde zunächst für Männer mit Androgen-entziehender Therapie wegen Prostatakrebs zuge lassen. Studienergebnisse der multizentrischen, kontrolliert randomisierten 2-Jahres-ADAMO-Studie werden vermutlich in Kürze eine generelle Zulassung für die Osteoporose des Mannes erlauben. Teriparatid, das 1–34-amino-terminale Ende des Parathormons, ist auf der Basis verschiedener Studien als osteoanabole Substanz für Männer zugelassen. Unter den Substanzen mit anderen Wirkmechanismen kann das D-Hormon-Prodrug Alfacalcidol allein oder in Kombination mit Bisphosphonaten eingesetzt werden und dabei pleiotrope Effekte auf Kalziumresorption, Nebenschilddrüsen, Muskel und Knochen entfalten. Auch Strontiumranelat wurde für die Osteoporose bei Männern zugelassen, jedoch neuerdings mit einer Kontraindikation für Patienten mit klinisch relevanten kardiovaskulären Risiken. Insgesamt haben sich somit in den vergangenen Jahren die therapeutischen Möglichkeiten für Männer mit Osteoporose deutlich gebessert. Durch ein verfügbares Spektrum von milden bis hin zu starken Substanzen mit unterschiedlichem Wirkprofil auf den Knochenumbau ist die Option individuell angepasster Therapiestrategien verbessert worden.

Keywords

Osteoporosis in men - treatment/management of male osteoporosis

Schlüsselwörter

Osteoporose des Mannes - Behandlung/Management der Osteoporose beim Mann

• References

• 1 Nguyen TV, Center JR, Eisman JA. Osteoporosis: underrated, under-diagnosed and undertreated. Med J Aust 2004; 180 (5 Suppl) 18-22.
• 2 Ringe JD. Treatment of osteoporosis in men. JMHG 2007; 4: 326-333.
• 3 Ringe JD. Osteoporosis in men. Medicographia 2010; 32: 71-78.
• 4 Johnell O, Kanis JA. An estimate of the worldwide prevalence of disability associated with osteoporotic fractures. Osteoporos Int 2006; 17: 1726-1733.
• 5 Haentjens P, Magaziner J, Colon Emeric. Meta-analysis: excess mortality after hip fracture among older women and men. Ann Intern Med 2010; 152: 380-390.
• 6 Swislocki A, Green JA, Heinrich G. Prevalence of osteoporosis in men in a VA rehabilitation center. Am J Manag Care 2010; 16: 427-433.
• 7 Olszynski WP. Osteoporosis in men: epidemiology, diagnosis, prevention, and treatment. Clin Ther 2004; 26: 15-28.
• 8 Kiebzak GM. Undertreatment of osteoporosis in men with hip fracture. Arch Intern Med 2002; 162: 2217-2222.
• 9 Donaldsen MG, Cawthon PM, Lui LY. Estimates of the proportion of older white men who would be recommended for pharmacologic treatment by the new US National Osteoporosis Foundation guidelines. J Bone Miner Res 2010; 25: 1506-1511.
• 10 Ringe JD. Osteoporosis in Men. In: Hosking D, Ringe J. eds. Treatment of metabolic bone disease. Management strategy and drug therapy. London: Martin Dunitz; 2000
• 11 Amin S, Felson DT. Osteoporosis in men. Osteoporos Int 2001; 27: 19-47.
• 12 Orwoll E, Klein R. Osteoporosis in men. San Diego/USA: Academic Press; 2001
• 13 Ringe JD, Dorst AJ, Faber H. Osteoporosis in men – Clinical assessment of 400 patients and 205 controls by risk factor analysis, densitometry, and x.ray findings. Osteologie 1997; 6: 81-86.
• 14 Pietschmann F, Breslau NA, Pak CYC. Reduced vertebral bone density in hypercalciuric nephrolithiasis. J Bone Miner Res 1992; 7: 1383-1388.
• 15 Ringe JD. Osteoporose des Mannes. Dtsch med Wschr 2003; 128: 925-928.
• 16 Habib GS, Haj S. Bone mineral density in patients with early rheumatoid arthritis treated with corticoids. Clin Rheumatol 2005; 24: 129-133.
• 17 Finkelstein JS, Klibanski A, Neer RM. et al. Increases in bone density during treatment of men with idiopathic hypogonadotropic hypogonadism. J Clin Endocrinol Metab 1989; 69: 776-783.
• 18 Snyder PJ, Wang C, Swerdloff RS. et al. Effects of testosterone replacement in hypogonadal men. J Clin Endocrinol Metab 2000; 85: 2670-2677.
• 19 Wang C, Swerdloff RS, Iranmanes A. et al. Effects of transdermal testosterone gel on bone turnover markers and bone mineral density in hypogonadal men. Clin. Endocrinol 2001; 54: 739-750.
• 20 Ringe JD, Schacht E. Potential of alfacalcidol for reducing increased risk of falls and fractures. Rheumatol Internat 2009; 29: 1177-1185.
• 21 Dukas L, Schacht E, Runge M, Ringe JD. Effect of a six-month therapy with alfacalcidol on muscle power and balance and the number of fallers and falls. Drug Research 2010; 60: 519-525.
• 22 Orwoll E, Ettinger M, Weiss S. et al. Alendronate for the treatment of osteoporosis in men. N Engl J Med 2000; 343: 604-610.
• 23 Ringe JD, Dorst A, Faber H, Ibach K. Alendonate treatment of established primary osteoporosis in men: 3-year results of a prospective, comparative, two-arm study. Rheumatology Int 2004; 24: 110-113.
• 24 Ringe JD, Orwoll E, Daifotis A, Lombardi A. Treatment of male osteoporosis: Recent advances with alendronate. Osteoporos Int 2002; 13: 195-199.
• 25 Reid DM. et al. Risedronate increases bone density and reduces vertebral fracture risk within one year in men on corticosteroid therapy. Calcif Tissue Int 2001; 69: 242-247.
• 26 Ringe JD, Faber H, Farahmand P, Dorst A. Efficacy of risedronate in men with primary and secondary osteoporosis. Results of a 1-year study. Rheumatol Int 2006; 26: 427-431.
• 27 Ringe JD, Farahmand P, Faber H, Dorst A. Sustained efficacy of risedronate in men with primary and secondary osteoporosis: results of a 2-year study. Rheumatol Int 2009; 29: 311-315.
• 28 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.
• 29 Orwoll E, Blinkley NC, Lewiecki EM. et al. Efficacy and safety of monthly ibandronate in menwith low bone density. Bone 2010; 46: 970-976.
• 30 Fahrleitner-Pammer A, Piswanger-Soelkner C, Pieber TR. et al. Ibandronate prevents bone loss and reduces vertebral fractures risk in male cardiac transplant patients: A randomized double-blind, placebo-controlled trial. J Bone Miner Res 2009; 24: 1335-1343.
• 31 Lyles KW, Colon-Emeric CS, Magaziner JS. et al. Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med 2007; 357: 1799-1809.
• 32 Boonen S, Orwoll E, Magaziner J. et al. Once-Yearly Zoledronic Acid in Older Men Compared with Women with Recent Hip Fracture. J Am Geriatr Soc 2011; 59: 2084-2090.
• 33 Boonen S, Reginster JY, Kaufman JM. et al. Fracture risk reduction and zoledronic acid therapy in men with osteoporosis. N Engl J Med 2012; 367: 1714-1723.
• 34 Cummings SR, San Martin J, McClung MR. et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 2009; 361: 756-765.
• 35 Smith MR, Saad F, Egerdie B. et al. Effects of denosumab on bone mineral density in men receivung androgen deprivation therapy for prostate cancer. J Urol 2009; 182: 2670-2675.
• 36 Ringe JD, Farahmand P. Improved Real-life Adherence of 6-monthly Denosumab Injections due to Positive Feedback based on Rapid 6-months BMD Increase and Good Safety Profile. Rheumtol Int. DOI 10.1007/s00 296 012-2663-2.
• 37 Orwoll E, Teglbjaerg 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.
• 38 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.
• 39 Tashjian Jr. AH, Chabner BA. Commentary on clinical safety of recombinant human parathyroid hormone 1-34 in the treatment of osteoporosis in men and postmenopausal women. J Bone Miner Res 2002; 17: 1151-1161.
• 40 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.
• 41 Leder BZ, Neer RM, Wyland JJ. et al. Effects of teriparatide treatment and discontinuation in postmenopausal women and eugonadal men with osteoporosis. J Clin Endocrinol Metab 2009; 94: 2915-2921.
• 42 Ringe JD, Dorst A, Farahmand P. Efficacy of strontium ranelate on bone mineral density in men with osteoporosis. Drug Research/Arzneimittelforschung 2010; 60: 267-272.
• 43 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.
• 44 Reginster JY, Kuntz D, Verdickt W. et al. Prophylactic use of alfacalcidol in corticosteroid-induced osteoporosis. Osteoporos Int 1999; 9: 75-81.
• 45 Sambrook PN, Birmingham J, Kelly PJ. et al. Prevention of corticosteroid osteoporosis: A comparison of calcium, calcitriol and calcitonin. N Engl J Med 1993; 328: 1747-1752.
• 46 Sambrook PN, Henderson NK, Keogh A. et al. Effect of Calcitriol on Bone Loss After Cardiac or Lung Transplantation. J Bone Miner Res 2000; 15: 1818-1824.
• 47 Ringe JD, Dorst A, Faber H. et al. Superiority of alfacalcidol over plain vitamin D in the treatment of glucocorticoid-induced osteoporosis. Rheumatol Int 2004; 24: 63-70.
• 48 Ringe JD. Alfacalcidol in men with osteoporosis: a prospective, observational study on 214 patients. Rheumatol Int. DOI 10.1007/s00296-012-2492-x.