BoneKEy-Osteovision | Commentary
Prevention of drug-induced osteoporosis: A new challenge
DOI:10.1138/2001045
Drug-induced bone diseases, and specifically osteoporosis, are a new form of osteopathy, as side effects of new treatments for chronic diseases (). Glucocorticoid-osteoporosis is the paradigm of these complications (). And remember, male gender is the most frequent presentation in these cases…!
GnRH analogs have been used alone or as coadjuvant therapy for several diseases, such as symptomatic endometriosis, endometrial carcinoma, leiomyomata uteri, uterine fibroids, polycystic ovary disease, dysfunctional uterine bleeding, paraphilia, congenital adrenal hyperplasia, and central or idiopathic precocious puberty. In recent years, GnRH analogs have also been used as the mainstay of treatment for metastatic prostate cancer (), the most common cancer and the second leading cause of death from cancer among men. With this treatment there occurs a decrease in bone mineral density (), an increase in markers of bone resorption (urinary N-telopeptide) and bone formation (bone-specific alkaline phosphatase) () and an increase in the risk of bone fractures (). The effect of GnRH analogs on bone has been linked to changes in skeletal sensitivity to parathyroid hormone () and the metabolic effects of estrogen suppression in males ().
Agents proposed for prevention of bone loss during GnRH treatment include herbal medicine for symptoms () and ipriflavone () or vitamin K2, which when combined with 1,25-(OH)2D3, can partially revert bone loss (). Calcium supplements, if used from the beginning (), and PTH () are also effective. Recently, in a 48-week, open-labeled study, 47 men with advanced or recurrent prostate cancer and no bone metastases were randomly assigned to receive either leuprolide alone (22.5 mg given intramuscularly every 12 weeks) or 3-month depot leuprolide and pamidronate disodium (60 mg intravenously every 12 weeks). 41 men completed the study. Serious adverse events occurred in eight men but were not necessarily related to the therapy. There were significant differences between the two groups in the mean changes in bone mineral density measured by dual-energy x-ray absorptiometry at 48 weeks in the lumbar spine (P<0.001), trochanter (P=0.003), total hip (P=0.005) and in trabecular bone of the lumbar spine (P=0.02) measured by quantitative computed tomography (). This finding is consistent with previous observations that bisphosphonates reduce bone loss in men and women receiving bone-losing drugs, including glucocorticoids.
The limitations of this study include the open-label design that may have affected subjective end points, such as the reported adverse events and that most of the men were white, so the benefits of pamidronate might not occur in other racial groups. These findings must be confirmed with larger studies to determine whether pamidronate treatment decreases the incidence of bone fractures.
Other questions arise: In all patients receiving long-term GnRH analogs for prostate cancer, is there a need to measure bone mineral density and bone metabolic markers periodically? Or to evaluate secondary osteoporosis? Or to initiate an active preventive pharmacological treatment? Perhaps it will be wise, as happens in patients with long-term glucocorticoid treatment () to recommend physical activity and nutritional measurements in all patients, to avoid causes of bone loss such as tobacco, high alcohol intake and in older patients to take measures to prevent falls. And in cases with risk factors for osteoporosis, after densitometric evaluation, it may be appropriate to initiate anti-resorbing drugs to prevent further bone loss. Certainly, drug-induced osteoporosis is a new challenge and a new economic burden in the management of our patients, including men.
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