The Effects of Intravenous Pamidronate on the Bone Tissue of Children and Adolescents with Osteogenesis Imperfecta

Overview

Journal J Clin Invest

Specialty General Medicine

Date 2002 Nov 6

PMID 12417568

Citations 84

Authors

Frank Rauch

Rose Travers

Horacio Plotkin

Francis H Glorieux

Affiliations

Soon will be listed here.

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.

Citing Articles

Bone Health in Paediatric Inflammatory Bowel Disease.

Sen P, Uday S Diagnostics (Basel). 2025; 15(5).

PMID: 40075827 PMC: 11899547. DOI: 10.3390/diagnostics15050580.

Improvement of bone properties in children with osteogenesis imperfecta after pamidronate: a bone biopsy study.

Farlay D, Cornier M, Rizzo S, Cormier-Daire V, Charpie M, Pinto G JBMR Plus. 2025; 9(2):ziae161.

PMID: 39822213 PMC: 11736749. DOI: 10.1093/jbmrpl/ziae161.

Osteoclast indices in osteogenesis imperfecta: systematic review and meta-analysis.

Aksornthong S, Patel P, Komarova S JBMR Plus. 2024; 8(11):ziae112.

PMID: 39372603 PMC: 11450326. DOI: 10.1093/jbmrpl/ziae112.

Approach to the Pediatric Patient With Glucocorticoid-Induced Osteoporosis.

Ward L, Bakhamis S, Bakhamis S, Koujok K J Clin Endocrinol Metab. 2024; 110(2):572-591.

PMID: 39126675 PMC: 11747689. DOI: 10.1210/clinem/dgae507.

A practical guide to the diagnosis and management of osteoporosis in childhood and adolescence.

Ward L Front Endocrinol (Lausanne). 2024; 14:1266986.

PMID: 38374961 PMC: 10875302. DOI: 10.3389/fendo.2023.1266986.

References

Burr D . Targeted and nontargeted remodeling. Bone. 2002; 30(1):2-4. DOI: 10.1016/s8756-3282(01)00619-6. View

Glorieux F, Ward L, Rauch F, Lalic L, Roughley P, Travers R . Osteogenesis imperfecta type VI: a form of brittle bone disease with a mineralization defect. J Bone Miner Res. 2002; 17(1):30-8. DOI: 10.1359/jbmr.2002.17.1.30. View

Reid I, Brown J, Burckhardt P, Horowitz Z, Richardson P, Trechsel U . Intravenous zoledronic acid in postmenopausal women with low bone mineral density. N Engl J Med. 2002; 346(9):653-61. DOI: 10.1056/NEJMoa011807. View

Astrom E, Soderhall S . Beneficial effect of long term intravenous bisphosphonate treatment of osteogenesis imperfecta. Arch Dis Child. 2002; 86(5):356-64. PMC: 1751119. DOI: 10.1136/adc.86.5.356. View

Ward L, Rauch F, Travers R, Chabot G, Azouz E, Lalic L . Osteogenesis imperfecta type VII: an autosomal recessive form of brittle bone disease. Bone. 2002; 31(1):12-8. DOI: 10.1016/s8756-3282(02)00790-1. View

Hamill P, Drizd T, Johnson C, Reed R, Roche A, MOORE W . Physical growth: National Center for Health Statistics percentiles. Am J Clin Nutr. 1979; 32(3):607-29. DOI: 10.1093/ajcn/32.3.607. View

Sillence D, Senn A, Danks D . Genetic heterogeneity in osteogenesis imperfecta. J Med Genet. 1979; 16(2):101-16. PMC: 1012733. DOI: 10.1136/jmg.16.2.101. View

Parfitt A, Drezner M, Glorieux F, Kanis J, MALLUCHE H, Meunier P . Bone histomorphometry: standardization of nomenclature, symbols, and units. Report of the ASBMR Histomorphometry Nomenclature Committee. J Bone Miner Res. 1987; 2(6):595-610. DOI: 10.1002/jbmr.5650020617. View

Frost H . Skeletal structural adaptations to mechanical usage (SATMU): 1. Redefining Wolff's law: the bone modeling problem. Anat Rec. 1990; 226(4):403-13. DOI: 10.1002/ar.1092260402. View

10.

Carter D, Bouxsein M, Marcus R . New approaches for interpreting projected bone densitometry data. J Bone Miner Res. 1992; 7(2):137-45. DOI: 10.1002/jbmr.5650070204. View

11.

Ganguly A, Rock M, Prockop D . Conformation-sensitive gel electrophoresis for rapid detection of single-base differences in double-stranded PCR products and DNA fragments: evidence for solvent-induced bends in DNA heteroduplexes. Proc Natl Acad Sci U S A. 1993; 90(21):10325-9. PMC: 47767. DOI: 10.1073/pnas.90.21.10325. View

12.

Bollen A, Eyre D . Bone resorption rates in children monitored by the urinary assay of collagen type I cross-linked peptides. Bone. 1994; 15(1):31-4. DOI: 10.1016/8756-3282(94)90888-5. View

13.

Fazzalari N, Moore A, Byers S, Byard R . Quantitative analysis of trabecular morphogenesis in the human costochondral junction during the postnatal period in normal subjects. Anat Rec. 1997; 248(1):1-12. DOI: 10.1002/(SICI)1097-0185(199705)248:1<1::AID-AR1>3.0.CO;2-Z. View

14.

Burr D, Forwood M, Fyhrie D, Martin R, Schaffler M, Turner C . Bone microdamage and skeletal fragility in osteoporotic and stress fractures. J Bone Miner Res. 1997; 12(1):6-15. DOI: 10.1359/jbmr.1997.12.1.6. View

15.

Chavassieux P, Arlot M, Reda C, Wei L, Yates A, Meunier P . Histomorphometric assessment of the long-term effects of alendronate on bone quality and remodeling in patients with osteoporosis. J Clin Invest. 1997; 100(6):1475-80. PMC: 508326. DOI: 10.1172/JCI119668. View

16.

Chapurlat R, Delmas P, Liens D, Meunier P . Long-term effects of intravenous pamidronate in fibrous dysplasia of bone. J Bone Miner Res. 1997; 12(10):1746-52. DOI: 10.1359/jbmr.1997.12.10.1746. View

17.

Pataki A, Muller K, Green J, Ma Y, Li Q, Jee W . Effects of short-term treatment with the bisphosphonates zoledronate and pamidronate on rat bone: a comparative histomorphometric study on the cancellous bone formed before, during, and after treatment. Anat Rec. 1998; 249(4):458-68. DOI: 10.1002/(SICI)1097-0185(199712)249:4<458::AID-AR5>3.0.CO;2-N. View

18.

Korkko J, Ala-Kokko L, De Paepe A, Nuytinck L, Earley J, Prockop D . Analysis of the COL1A1 and COL1A2 genes by PCR amplification and scanning by conformation-sensitive gel electrophoresis identifies only COL1A1 mutations in 15 patients with osteogenesis imperfecta type I: identification of common sequences of.... Am J Hum Genet. 1998; 62(1):98-110. PMC: 1376813. DOI: 10.1086/301689. View

19.

Fleisch H . Bisphosphonates: mechanisms of action. Endocr Rev. 1998; 19(1):80-100. DOI: 10.1210/edrv.19.1.0325. View

20.

Glorieux F, Bishop N, Plotkin H, Chabot G, Lanoue G, Travers R . Cyclic administration of pamidronate in children with severe osteogenesis imperfecta. N Engl J Med. 1998; 339(14):947-52. DOI: 10.1056/NEJM199810013391402. View