Long-term effects of bisphosphonates on the growing skeleton. Studies of young patients with severe osteoporosis.
Osteoporosis in children and adolescents is relatively uncommon and usually secondary to identifiable causal factors. There are no generally accepted therapies for patients with no treatable underlying cause of disease. Any treatment of young patients with bone-acting compounds should be not only effective but also devoid of adverse effects on bone growth and remodeling. For many years we have been studying the effects of bisphosphonates-an effective treatment of postmenopausal osteoporosis-on the growing skeleton. We review here our experience in the treatment of young patients with osteoporosis with special emphasis on issues of skeletal safety and effectiveness, and we discuss the available literature data. We studied 12 patients aged between 10.7 and 17.2 years with symptomatic osteoporosis and multiple fractures treated with the bisphosphonates pamidronate or olpadronate for periods between 2 and 8 years continuously. Linear growth continued normally on treatment; there was even a catch-up growth in prepubertal patients, and there was no excessive suppression of bone remodeling, assessed biochemically. Bone biopsies obtained at various stages during treatment showed bone of normal lamellar structure without mineralization defects. There was an increase in calcium balance, already evident within 10 days, the level of which was maintained for at least 3 years of treatment. This was associated with progressive increases in bone mineral density along a different slope from that of healthy peers as well as correction of vertebral deformities on X-rays in patients given bisphosphonates before puberty. Treatment was well tolerated and clinical improvement was remarkable. Our studies, supported by literature data, strongly suggest that bisphosphonate therapy can be beneficial to young patients with osteoporosis for whom no other options are currently available, and justify planning controlled studies in more common conditions for which no treatment is currently available, such as osteogenesis imperfecta.
Brumsen
C
C
Department of Endocrinology and Metabolic Diseases, University Hospital, Leiden, The Netherlands.
Hamdy
N A
NA
Papapoulos
S E
SE
D000293:Adolescent; D015519:Bone Density; D001846:Bone Development / Q000187:drug effects*; D002118:Calcium / Q000627:therapeutic use; D002648:Child; D004164:Diphosphonates / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D010024:Osteoporosis / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D012189:Retrospective Studies; D012720:Severity of Illness Index; D014807:Vitamin D / Q000097:blood
D004164:Diphosphonates; D014807:Vitamin D; D002118:Calcium