Intravenous pamidronate treatment of infants with severe osteogenesis imperfecta

Abstract

Objective: Children with the severe forms of osteogenesis imperfecta have in several studies been treated with intravenous pamidronate, but there are only few reports of the effect of early treatment. Aim: To evaluate the effect of treatment started in infancy. Methods: In a prospective observational study, with a historic control group, intravenous disodium pamidronate (APD) was given as monthly infusions to 11 children with osteogenesis imperfecta aged 3-13 (median 3.6) months, who had severe osteogenesis imperfecta with congenital bowing of the femora and vertebral compression fractures. Results: During treatment of children aged between 3 and 6 (median 4.5) years, dual-energy x ray absorptiometry measurements of the lumbar spine showed a gradual increase in bone density. Bone metabolism parameters in serum (alkaline phosphatase, osteocalcin, procollagen 1 carboxy-terminal peptide, collagen 1 teleopeptide) and in urine (deoxypyridinoline) indicated a decrease in bone turnover. An improvement of mobility was seen and at the latest recording, at the age of 3.3-6.5 (median 4.8) years, the children could all walk. Vertebral remodelling was seen, with increased vertebral height, and no child developed scoliosis, kyphosis or basilar impression. All children required femoral intramedullar rods for fractures, and five needed tibial rodding for extreme curvatures that prevented functional standing and walking. No adverse effects were seen on growth, fracture healing or blood chemistry. Conclusions: APD is an efficient symptomatic treatment for infants with severe osteogenesis imperfecta, but additional orthopaedic surgery is often needed. Early treatment may prevent scoliosis and basilar impression. Long-term follow-up is important.

Bisphosphonate treatment for type III osteogenesis imperfecta in Lady Ridgeway Hospital, Colombo, Sri Lanka

“…The efficacy of the drug is comparable to that in other studies in Sri Lanka and elsewhere 3,4,5,7 .…”

“…In a similar prospective observational study 4 , with a historic control group, intravenous pamidronate was given as monthly infusions to 11 children with severe OI aged 3-13 (median 3.6) months. During treatment of children aged between 3 and 6 (median 4.5) years, dual-energy x ray absorptiometry measurements of the lumbar spine showed a gradual increase in bone density.…”

“…Current therapeutic options include growth hormone, bisphosphonates, gene therapy and bone marrow transplantation. There have been promising results with cyclical administration of bisphosphonates, especially intravenous pamidronate in children with OI, from neonatal age up to adolescence 2,3,4,5,7 . The mechanism of action of bisphosphonates is inhibition of the osteoclastic activity.…”

THERAPY OF ENDOCRINE DISEASE: Treatment of osteogenesis imperfecta in adults

“…Infants as young as 2 months have been treated with promising results and safety data (59,60,61,75), and according to one study younger children did not gain as much bone compared with older children, explained by the fact that the deficit in BMD was smaller in younger children (67). Another study considered the response in infants to be faster and more pronounced than that in older children (75).…”

“…Individuals with mild OI are treated conservatively in most centers. In moderateto-severe cases, with multiple long-bone fractures and/or vertebral compression fractures, bisphosphonate treatment is being used in children and often initiated at a young age, even in infancy (59,60,61,62,63). However, considerably less is known about how best to treat adults with moderate-to-severe OI, as only few trials, each comprising small numbers of treated patients with different OI types, have been published.…”