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Pamidronate treatment of osteogenesis imperfecta--lack of correlation between clinical severity, age at onset of treatment, predicted collagen mutation and treatment response.
J Pediatr Endocrinol Metab. 2002 Feb; 15(2):163-74.JP

Abstract

Severe forms of osteogenesis imperfecta (OI) are characterised by osteoporosis with multiple fractures, deformity, progressive loss of mobility and chronic bone pain. Bisphosphonates, as osteoclast inhibitors, reduce bone turnover and improve osteoporosis.

OBJECTIVE

To investigate the effect of pamidronate treatment of severe OI in children, and find any correlation between clinical severity, age at start of treatment, type of predicted collagen mutation and treatment response.

DESIGN

Open, observational trial.

PATIENTS

A two-year study of pamidronate treatment was undertaken in a cohort of 18 children, (1.4-14.5 years) with OI types III and IV.

INTERVENTIONS

Disodium pamidronate, 1 mg/kg/day for 3 days every 4 months, by i.v. infusion with measurement of bone turnover, bone density, vertebral morphology and skin biopsies to assess collagen mutation.

RESULTS

Eleven children have completed 2 years of treatment and three more have completed 20 months. Sustained cessation of bone pain, improved mobility and decreased fracture rate were seen in all patients. Bone turnover decreased slightly but was not statistically significant. Bone mineral density (BMD) of lumbar spine increased by a mean of 124.7 +/- 75.7% over 2 years (Z score mean -5.08 +/- 1.27, to -3.30 +/- 1.71, p <0.001); the greatest change in BMD was seen in the most severely affected patients: 138 +/- 50.6% (severe), 62.47 +/- 22.9% (mild). There was a mean increase in vertebral height at L4 of 68.5% and in vertebral area of 85.4%. The majority of patients had slow electrophoretic migration of type I collagen alpha chains or reduced secretion of type I collagen, indicative of structural, helix-breaking mutations. There was no correlation between phenotypic severity, age at start of treatment and treatment response (r2 = 0.14)

CONCLUSIONS

Pamidronate treatment of severe forms of OI is an effective therapeutic modality to increase bone density, decrease fracture rate, increase mobility and improve quality of life, irrespective of the severity of the mutation or clinical phenotype. It has a good short-term safety profile.

Authors+Show Affiliations

Department of Endocrinology and Diabetes, Royal Children's Hospital, Parkville, Victoria, Australia. zacharim@cryptic.rch.unimelb.edu.auNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article

Language

eng

PubMed ID

11874181

Citation

Zacharin, Margaret, and John Bateman. "Pamidronate Treatment of Osteogenesis Imperfecta--lack of Correlation Between Clinical Severity, Age at Onset of Treatment, Predicted Collagen Mutation and Treatment Response." Journal of Pediatric Endocrinology & Metabolism : JPEM, vol. 15, no. 2, 2002, pp. 163-74.
Zacharin M, Bateman J. Pamidronate treatment of osteogenesis imperfecta--lack of correlation between clinical severity, age at onset of treatment, predicted collagen mutation and treatment response. J Pediatr Endocrinol Metab. 2002;15(2):163-74.
Zacharin, M., & Bateman, J. (2002). Pamidronate treatment of osteogenesis imperfecta--lack of correlation between clinical severity, age at onset of treatment, predicted collagen mutation and treatment response. Journal of Pediatric Endocrinology & Metabolism : JPEM, 15(2), 163-74.
Zacharin M, Bateman J. Pamidronate Treatment of Osteogenesis Imperfecta--lack of Correlation Between Clinical Severity, Age at Onset of Treatment, Predicted Collagen Mutation and Treatment Response. J Pediatr Endocrinol Metab. 2002;15(2):163-74. PubMed PMID: 11874181.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pamidronate treatment of osteogenesis imperfecta--lack of correlation between clinical severity, age at onset of treatment, predicted collagen mutation and treatment response. AU - Zacharin,Margaret, AU - Bateman,John, PY - 2002/3/5/pubmed PY - 2002/8/24/medline PY - 2002/3/5/entrez SP - 163 EP - 74 JF - Journal of pediatric endocrinology & metabolism : JPEM JO - J Pediatr Endocrinol Metab VL - 15 IS - 2 N2 - UNLABELLED: Severe forms of osteogenesis imperfecta (OI) are characterised by osteoporosis with multiple fractures, deformity, progressive loss of mobility and chronic bone pain. Bisphosphonates, as osteoclast inhibitors, reduce bone turnover and improve osteoporosis. OBJECTIVE: To investigate the effect of pamidronate treatment of severe OI in children, and find any correlation between clinical severity, age at start of treatment, type of predicted collagen mutation and treatment response. DESIGN: Open, observational trial. PATIENTS: A two-year study of pamidronate treatment was undertaken in a cohort of 18 children, (1.4-14.5 years) with OI types III and IV. INTERVENTIONS: Disodium pamidronate, 1 mg/kg/day for 3 days every 4 months, by i.v. infusion with measurement of bone turnover, bone density, vertebral morphology and skin biopsies to assess collagen mutation. RESULTS: Eleven children have completed 2 years of treatment and three more have completed 20 months. Sustained cessation of bone pain, improved mobility and decreased fracture rate were seen in all patients. Bone turnover decreased slightly but was not statistically significant. Bone mineral density (BMD) of lumbar spine increased by a mean of 124.7 +/- 75.7% over 2 years (Z score mean -5.08 +/- 1.27, to -3.30 +/- 1.71, p <0.001); the greatest change in BMD was seen in the most severely affected patients: 138 +/- 50.6% (severe), 62.47 +/- 22.9% (mild). There was a mean increase in vertebral height at L4 of 68.5% and in vertebral area of 85.4%. The majority of patients had slow electrophoretic migration of type I collagen alpha chains or reduced secretion of type I collagen, indicative of structural, helix-breaking mutations. There was no correlation between phenotypic severity, age at start of treatment and treatment response (r2 = 0.14) CONCLUSIONS: Pamidronate treatment of severe forms of OI is an effective therapeutic modality to increase bone density, decrease fracture rate, increase mobility and improve quality of life, irrespective of the severity of the mutation or clinical phenotype. It has a good short-term safety profile. SN - 0334-018X UR - https://www.unboundmedicine.com/medline/citation/11874181/Pamidronate_treatment_of_osteogenesis_imperfecta__lack_of_correlation_between_clinical_severity_age_at_onset_of_treatment_predicted_collagen_mutation_and_treatment_response_ L2 - https://www.degruyter.com/document/doi/10.1515/jpem.2002.15.2.163 DB - PRIME DP - Unbound Medicine ER -