The effects of intravenous pamidronate on the bone tissue of children and adolescents with osteogenesis imperfecta

Abstract

Cyclical pamidronate infusions increase bone mass in children suffering from osteogenesis imperfecta. The histological basis for these effects remains unknown. Therefore, we compared parameters of iliac bone histomorphometry from 45 patients before and after 2.4 ± 0.6 years of pamidronate treatment (age at the time of the first biopsy, 1.4-17.5 years; 23 girls). Although biopsy size did not change significantly (P = 0.30), cortical width increased by 88%. Cancellous bone volume increased by 46%. This was due to a higher trabecular number, whereas trabecular thickness remained stable. Bone surface-based indicators of cancellous bone remodeling decreased by 26-75%. There was no evidence for a mineralization defect in any of the patients. These results suggest that, in the growing skeleton, pamidronate has a twofold effect. In remodeling, bone resorption and formation are coupled and consequently both processes are inhibited. However, osteoclasts and osteoblasts are active on different surfaces (and are thus uncoupled) during modeling of cortical bone. Therefore resorption is selectively targeted, and continuing bone formation can increase cortical width.

Osteoporosis due to Glucocorticoid Use in Children with Chronic Illness

“…Intravenous pamidronate has been shown in a number of observational and case-control studies to benefit children with moderate-to-severe OI by improving pain, mobility, grip force, bone mass, and by decreasing the number of fractures [85,86,87,88,89,90]. The beneficial effect of pamidronate at the bone tissue level appears to be due to expansion of cortical width through selective inhibition of resorption during the modeling process [91]. …”

Pamidronate Treatment of Children with Moderate-to-Severe Osteogenesis Imperfecta: A Note of Caution

“…However, half our patients with nonunion experienced little or no improvement in their mobility scores. Our results suggest a need for minimizing delayed healing by assaying bone markers before and after pamidronate infusions [30, 31]. …”

Treatment of Osteogenesis Imperfecta: Who, Why, What?

“…The amount of trabecular bone also increased, which was due to a higher number of trabeculae [18]. With regard to long-term safety, no negative effect of pamidronate on renal function or growth has been detected in children with moderate to severe OI [12, 14, 19].…”

“…Indeed, promising results were reported in a small group of patients who received pamidronate in the first 2 years of life [13]. The effect of bisphosphonates on the skeleton is clearly growth-dependent [18]. Thus, postpubertal adolescents and adults cannot be expected to benefit as much as younger patients do.…”

“…For example, the age-specific Z-score for lumbar spine BMD increased by 2.0 during the first 2 years of treatment, but only by 0.6 between 2 and 4 years of treatment. Similarly, histomorphometric studies have shown that the cortical width of the iliac bones almost doubles during the first 2.4 years of pamidronate treatment, but changes little when therapy is continued for another 3 years thereafter [18]. …”