Drug products: 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 code: M05BA04, M05BB03
Substances: alendronate sodium, alendronate sodium anhydrous, alendronate sodium monohydrate
Bisphosphonate therapy increases bone mineral density (BMD) and decreases fracture risk to a similar extent in both men and women.
Results from one study showed that the effect of 5 and 10 mg alendronate in women with postmenopausal hormonal replacement therapy (HRT) and men did not differ. The recommended dose in Sweden is 10 mg/day.
Based on long-term bisphosphonate studies, there is no clear evidence of sex differences in the risk of atypical femur fracture and osteonecrosis of the jaw. Men on long-term bisphosphonate therapy seem to have similar safety issues as postmenopausal women.
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 .
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].
A series of clinical trials (in total 16 men, 132 women) found that the bioavailability of alendronate is similar in men and postmenopausal women . 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 .
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 . 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].
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 .
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 . 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) . 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 .
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) .
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]) .
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 .
Specific for alendronate
A review report that the safety profile of alendronate in osteoporotic men is similar to that previously reported in postmenopausal women .
Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).
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 .
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 .
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) .
In an observational study using Hungarian national prescription data, male patients had disproportionately fewer bisphosphonate prescriptions for osteoporosis in all age groups .
Date of litterature search: 2020-06-11
Reviewed by: Carl-Olav Stiller
Approved by: Karin Schenck-Gustafsson