Placebo-controlled randomized controlled trials (RCTs) of etidronate, alendronate and risedronate analyzed by systematic review and meta-analysis have shown that they all increase bone mineral density (BMD) at the spine and hip in a dose-dependent manner. They consistently reduce the risk of vertebral fractures by 30-50% (10). Since subjects in clinical trials conducted to date may not represent the population of concern here, an individual approach to treatment is warranted.

Alendronate has been studied and increases BMD in men while significantly reducing fractures from 7.1% in the control arm to 0.8% in the treatment arm (33).

Orwoll (33) showed that alendronate reduced the rate of vertebral fractures in 241 men, but did not show any alteration in hip or extremity fractures. A large study of men on steroids showed that risedronate decreased vertebral fractures (34).

Diamond T (35) treated 12 men with TAB for 12 months and gave no treatment for bone loss in the first six months, then etridonate and calcium supplements. In the latter six months BMD significantly rose by 7.8%, compared to the initial six months. A later RCT by this author on 21 men showed significant reduction in bone loss with IV pamidronate (26).

Smith (29) also randomized 43 men to pamidronate or placebo and prevented the loss in bone density. He has gone on to do a similar randomized study of 106 men and found a significant increase of BMD with zoledronate 4mg vs loss of BMD for patients receiving placebo (19).

While there are studies showing that bisphosphonates increase BMD, there is as yet no study showing that bisphosphonates reduce fracture incidence in the setting of androgen ablation.

Glucocorticoid-induced osteoporosis perhaps provides a model of how to approach hypogonadal men. First is the matter of treatment of established osteoporosis, and secondly the prevention of osteoporosis (and its complications). Bisphosphonates are the only therapy shown to reduce vertebral fractures in glucocorticoid-induced osteoporosis, with a high level of evidence for alendronate, risedronate and etidronate (in order).

Overall, taking all the studies of bisphosphonates for osteoporosis, there is ample evidence of the reduction in fracture risk (33, 34, 36-50). The question remains whether the costs, drug benefits, and potential side effects for the individual patient mean that a given drug is utilized. This is at the discretion of the GP or specialist.