Bisphosphonates have been extensively used in adult osteoporosis with positive effects on bone fracture risk. Their use in younger patients has been limited by fear of adverse effects on a growing skeleton and their long-term permanence in bone tissue. However, after more than 10 years of use in severe conditions such as osteogenesis imperfecta, bisphosphonates have been shown to be quite safe. No adverse effects on growth, pubertal spurt and healing of fractures have been reported, even after a long follow-up. Bone biopsies of treated patients show normal bone structure and no mineralization defects (56). Typical radiological alterations in pre-pubertal patients are radiolucent sclerotic bands (57), but they do not appear to have clinical relevance. Bisphosphonate use is now growing also in young patients (58-60), even if careful selection of cases and strict monitoring is required.

Regarding the studies on low bone mass in rheumatic diseases, different compounds and dosages have been used. Intravenous alendronate, oral olpandronate, IV pamidronate, oral clodronate, or oral alendronate have been used in children/adolescents affected by rheumatic diseases (mainly JIA), in most cases treated with steroids. Some studies are limited to single patients or small series, while other studies considered slightly larger samples (61-63). All these studies demonstrated an increase in BMD and a positive effect on pain related to vertebral fractures, without significant untoward side effects. The largest published study available is still that on the use of oral alendronate in 38 children (64,65), which showed a BMD increase of +14.9 ± 9.8% on average (13 patients having attained normal range) and no new fractures after 12 months of therapy. The highest BMD increase was observed in the patients who had the pubertal spurt during the year of alendronate therapy. A significant decrease in bone resorption and bone formation markers was also observed in these patients.

Adverse effects of bisphosphonates have not been reported in greater frequency in adolescents than in adults. A mild flu-like syndrome may occur after IV administration, usually the first one only. Transient hypocalcemia and mild abdominal discomfort or dyspepsia are also occasional complaints. According to present knowledge, the use of bisphosphonates in pregnancy cannot be considered safe, since they are known to cross the placenta and could have effects on the fetal bones. If bisphosphonates are needed in a sexually active girl, contraceptive methods must be adopted.

In conclusion, all the published studies so far have consistently showed that bisphosphonates are effective in counteracting bone loss induced by rheumatic diseases and/or corticosteroid therapy in young patients. However, larger studies, particularly controlled with placebo, are needed.

The previous observations apply only to the correct, prudent use of appropriate drug doses on the basis of age and body weight. Whyte reported a case of frank misuse, with very high biophosphonate doses for a very long time, without adequate clinical, biochemical and densitometrical monitoring, which led to severe untoward effects (66). New administration schedules (e.g., once-a-week pills, once-a-month injections) may be appealing in order to improve the compliance and the quality of life, especially in adolescents.

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