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Alendronat

Klassificering: A

Preparat: ADROVANCE, Alenat, Alenat Veckotablett, Alendronat Accord Veckotablett, Alendronat Actavis Veckotablett, Alendronat Arrow, Alendronat Arrow Veckotablett, Alendronat Aurobindo Veckotablett, Alendronat Bluefish Veckotablett, Alendronat MDS Veckotablett, Alendronat Mylan, Alendronat Mylan Veckotablett, Alendronat Orifarm Veckotablett, Alendronat Ranbaxy Veckotablett, Alendronat ratiopharm Veckotablett, Alendronat Sandoz Veckotablett, Alendronat STADA, Alendronat STADA Veckotablett, Alendronat Teva, Alendronat Teva Veckotablett, Alendronat Unimedic, Alendronate/Cholecalciferol Accord, Alendronic Acid, Binosto, Fosamax, Fosamax Veckotablett, Fosamax®, Fosamax® Veckotablett, Fosastad, Fosavance®

ATC kod: M05BA04, M05BB03

Sammanfattning

Bisfosfonater ökar benmineraltätheten (BMD) lika effektivt och ger likartad lägre risk för fraktur hos både män och kvinnor..

En studie visade att kvinnor med postmenopausal hormonbehandling (HRT) och män hade lika bra effekt av 5 mg och 10 mg alendronat. I Sverige rekommenderas idag 10 mg/dag.

Det finns inte någon säkerställd könsskillnad i risken för atypiska femurfrakturer och käkosteonekros vid långtidsbehandling med bisfosfonater. Säkerhetspanoramat och risken för biverkningar vid långtidsbehandling med bisfosfonater hos män förefaller vara desamma som hos postmenopausala kvinnor.

Additional information

Female sex is one of the risk factors for osteoporosis fragility fractures. The same type of fractures occurs in men and women with osteoporosis. Women are more prone to spinal fractures, due to a relatively abrupt bone density loss after menopause. Men have a higher peak bone mass (in general), and the bone density deteriorates more successively from the age of 40 [1].

Osteoporosis in men is largely underdiagnosed and undertreated. Also, in those men with a history of fractures and a high risk of new fractures. Although there are differences between men and women in the pathophysiology of osteoporosis, such as in the pattern of bone loss, similarities like clinical risk factors predominate. Drug approval for osteoporosis treatment in men has generally been based on small-scale bridging trials with bone mineral density (BMD) endpoint for substances previously shown to reduce fracture risk in postmenopausal osteoporosis [2, 3].

Pharmacokinetics and dosing

A series of clinical trials (in total 16 men, 132 women) found that the bioavailability of alendronate is similar in men and postmenopausal women [11]. One clinical trial (141 men, 336 women) showed similar efficacy on increased BMD (bone mineral density) with 5 and 10 mg of alendronate in men and postmenopausal women with hormonal replacement therapy [12].

Effects

The mechanism of action of bisphosphonates is not believed to be different between men and women, and the results of bisphosphonate studies suggest similar efficacy in men and women [13]. Data from placebo-controlled clinical trials in primary and glucocorticoid-induced osteoporosis show an increase in lumbar spine BMD in men and women after 12 months of treatment with alendronate 10 mg/day [12, 14, 15]. A meta-analysis (in total 375 men) reports that alendronate 10 mg/day decreases the risk of vertebral fractures in men to a similar extent as previously  observed in postmenopausal women (in total 12698 women) [16, 17].

Adverse effects

Bisphosphonates

The data supporting the algorithm of long-term osteoporosis management with bisphosphonates, up to a total of 10 years, is described in a report by the American Society for Bone and Mineral Research (ASBMR) Task Force. The report stated that there is no evidence of sex differences in the risk of associated atypical femur fracture and osteonecrosis of the jaw from long-term bisphosphonate treatment. Men on long-term bisphosphonate therapy presumably have similar safety issues as postmenopausal women [4].

In a systematic review on the effect of anti-resorptive drugs on the development of medication-related osteonecrosis of the jaw in osteoporosis patients, patients’ sex was reported in 587 cases (38 men, 549 women). The majority of cases were found in women with a male-to-female ratio of 1:14 [5]. Another systematic review on medication-related osteonecrosis of the jaw from anti-resorptive drugs treatment found no significant interactions for patient’s sex (6 men, 53 women) [6]. The low number of men in these reviews does not allow any speculation on sex difference with regard to bisphosphonate-related osteonecrosis of the jaw.  In a survey sent to all oral and maxillofacial surgery clinics and hospital dental clinics in Sweden requesting reports of all new cases of bisphosphonate-related osteonecrosis of the jaw during 2007 and 2008, women accounted for 22 of the 26 oral bisphosphonate-related osteonecrosis of the jaw cases in 2007 and 25 of the 29 cases in 2008. Women were prescribed bisphosphonates 7.5 times more frequently than were men during 2007 and 2008 in Sweden. However, the number of men with osteonecrosis of the jaw was too few for a valid determination of the male incidence  [7]. 

Radiographs of Swedish women and men ≥55 years (n=5,342) with femoral shaft fractures during a 3-year period were reviewed. Atypical fractures were found in 12 men and 160 women. The age-adjusted relative risk (RR) of atypical fracture associated with bisphosphonate use was 55 (95% CI: 39-79) in women and 54 (CI: 15-92) in men. In bisphosphonate users, the risk of atypical fracture was higher in women than men (RR=3.1, CI:1.1-8.4) [8].

In a study evaluating oral bisphosphonates and reported clostridium difficile infection (CDI), CDI adverse drug reactions were more common for women (0.45% [93/20,586]) compared to men (0.25% [4/1568]) [9]. 

No sex differences were found in a population-based, international case-control study (134,475 men, 738,397 women) on the risk of valvulopathy among bisphosphonate users [10]. 

Specific for alendronate

A review report that the safety profile of alendronate in osteoporotic men is similar to that previously reported in postmenopausal women [18].

Reproductive health issues

Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).

Other information

A Norwegian study (1010 men, 6600 women) examined the influence of socioeconomic factors on adherence of alendronate drug treatment in patients 40-79 years old. In women, the most important factors for being adherent were age 60 years or more and high income. In men, a middle educational level predicted adherence [19].

The ASBMR Task Force report stated that continued treatment with bone protective therapy is indicated in women taking glucocorticoids long-term in a dose >5 mg/day of oral prednisolone or equivalent. Men ≥50 years who are treated with long-term glucocorticoids >5mg/day are also at increased risk of fracture and may benefit from continuation of therapy [4].

In a Spanish population-based cohort study trends of use of anti-osteoporosis drugs were analyzed. Out of 1.5 million participants, 135,410 received anti-osteoporosis drug treatment during 2001–2013. Prevalence was higher in women (6.1%) compared to men (1.1%). The incidence rate (IR) was 24.90 in women and 2.77 in men. IRs were highest for bisphosphonates along the years (ranging 3.70–14.73 and 0.57–1.75 in women and men respectively) [20].

In an observational study using Hungarian national prescription data, male patients had disproportionately fewer bisphosphonate prescriptions for osteoporosis in all age groups [21].

Försäljning på recept

Fler kvinnor än män hämtade ut tabletter innehållande alendronsyra (ATC-kod M05BA04) på recept i Sverige år 2019, totalt 62 938 kvinnor och 16 814 män. Det motsvarar 12 respektive 3 personer per tusen invånare. Andelen som hämtat ut läkemedel var högst i åldersgruppen 75 år och äldre hos båda könen. Totalt sett var tabletter innehållande alendronsyra 3,8 gånger vanligare hos kvinnor [22].

Hos individer över 50 år i Sverige har det uppskattats att 20 % av kvinnor och 2,5 % av män har behov av osteoporosläkemedel [23].

Uppdaterat: 2020-09-03

Litteratursökningsdatum: 2020-06-11

Referenser

  1. Läkemedelsverket. Läkemedel vid osteoporos för att förhindra benskörhetsfrakturer - behandlingsrekommendation. Läkemedelsverket [www]. [updated 2020-04-30, cited 2020-06-11]. länk
  2. Kaufman JM, Lapauw B, Goemaere S. Current and future treatments of osteoporosis in men. Best Pract Res Clin Endocrinol Metab. 2014;28(6):871-84. PubMed
  3. Adler RA. Update on osteoporosis in men. Best Pract Res Clin Endocrinol Metab. 2018;32(5):759-772. PubMed
  4. Adler RA, El-Hajj Fuleihan G, Bauer DC, Camacho PM, Clarke BL, Clines GA et al. Managing Osteoporosis in Patients on Long-Term Bisphosphonate Treatment: Report of a Task Force of the American Society for Bone and Mineral Research. J Bone Miner Res. 2016;31(1):16-35. PubMed
  5. Aljohani S, Fliefel R, Ihbe J, Kühnisch J, Ehrenfeld M, Otto S. What is the effect of anti-resorptive drugs (ARDs) on the development of medication-related osteonecrosis of the jaw (MRONJ) in osteoporosis patients: A systematic review. J Craniomaxillofac Surg. 2017;45(9):1493-1502. PubMed
  6. Khominsky A, Lim M. "Spontaneous" medication-related osteonecrosis of the jaw; two case reports and a systematic review. Aust Dent J. 2018;63(4):441-454. PubMed
  7. Ulmner M, Jarnbring F, Törring O. Osteonecrosis of the jaw in Sweden associated with the oral use of bisphosphonate. J Oral Maxillofac Surg. 2014;72(1):76-82. PubMed
  8. Schilcher J, Koeppen V, Aspenberg P, Michaëlsson K. Risk of atypical femoral fracture during and after bisphosphonate use. Acta Orthop. 2015;86(1):100-7. PubMed
  9. McConeghy KW, Soriano MM, Danziger LH. A Quantitative Analysis of FDA Adverse Event Reports with Oral Bisphosphonates and Clostridium difficile. Pharmacotherapy. 2016;36(10):1095-1101. PubMed
  10. Coloma PM, de Ridder M, Bezemer I, Herings RM, Gini R, Pecchioli S et al. Risk of cardiac valvulopathy with use of bisphosphonates: a population-based, multi-country case-control study. Osteoporos Int. 2016;27(5):1857-67. PubMed
  11. Gertz BJ, Holland SD, Kline WF, Matuszewski BK, Freeman A, Quan H et al. Studies of the oral bioavailability of alendronate. Clin Pharmacol Ther. 1995;58:288-98. PubMed
  12. Saag KG, Emkey R, Schnitzer TJ, Brown JP, Hawkins F, Goemaere S et al. Alendronate for the prevention and treatment of glucocorticoid-induced osteoporosis Glucocorticoid-Induced Osteoporosis Intervention Study Group. N Engl J Med. 1998;339:292-9. PubMed
  13. Bonnick SL. Osteoporosis in men and women. Clin Cornerstone. 2006;8:28-39. PubMed
  14. Ho YV, Frauman AG, Thomson W, Seeman E. Effects of alendronate on bone density in men with primary and secondary osteoporosis. Osteoporos Int. 2000;11:98-101. PubMed
  15. Iwamoto J, Takeda T, Sato Y, Uzawa M. Comparison of the effect of alendronate on lumbar bone mineral density and bone turnover in men and postmenopausal women with osteoporosis. Clin Rheumatol. 2007;26:161-7. PubMed
  16. Sawka AM, Papaioannou A, Adachi JD, Gafni A, Hanley DA, Thabane L. 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. PubMed
  17. Cranney A, Wells G, Willan A, Griffith L, Zytaruk N, Robinson V et al. Meta-analyses of therapies for postmenopausal osteoporosis II Meta-analysis of alendronate for the treatment of postmenopausal women. Endocr Rev. 2002;23:508-16. PubMed
  18. Ringe JD, Orwoll E, Daifotis A, Lombardi A. Treatment of male osteoporosis: recent advances with alendronate. Osteoporos Int. 2002;13:195-9. PubMed
  19. Devold HM, Furu K, Skurtveit S, Tverdal A, Falch JA, Sogaard AJ. Influence of socioeconomic factors on the adherence of alendronate treatment in incident users in Norway. Pharmacoepidemiol Drug Saf. 2012;21:297-304. PubMed
  20. Martín-Merino E, Huerta-Álvarez C, Prieto-Alhambra D, Montero-Corominas D. Cessation rate of anti-osteoporosis treatments and risk factors in Spanish primary care settings: a population-based cohort analysis. Arch Osteoporos. 2017;12(1):39. PubMed
  21. Bor A, Matuz M, Gyimesi N, Biczók Z, Soós G, Doró P. Gender inequalities in the treatment of osteoporosis. Maturitas. 2015;80(2):162-9. PubMed
  22. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2019 [cited 2020-03-10.] länk
  23. Svedbom A, Hernlund E, Ivergård M, Compston J, Cooper C, Stenmark J et al. Osteoporosis in the European Union: a compendium of country-specific reports. Arch Osteoporos. 2013;8:137. PubMed

Författare: Diana Rydberg, Linnéa Karlsson Lind

Faktagranskat av: Carl-Olav Stiller

Godkänt av: Karin Schenck-Gustafsson