Diphosphonate Treatment of Paget's Disease of Bone

J. Gunčaga; Th. Lauffenburger; Charlotte Lentner; M. A. Dambacher; H. G. Haas; H. Fleisch; A. J. Olah

doi:10.1055/s-0028-1093886

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 1974; 6(1): 62-69
DOI: 10.1055/s-0028-1093886

Originals

Diphosphonate Treatment of Paget's Disease of Bone

A correlated metabolic, calcium kinetic and morphometric study[*] [**] J. Gunčaga¹ , Th. Lauffenburger¹ , Charlotte Lentner¹ , M. A. Dambacher¹ , H. G. Haas¹ , H. Fleisch² , A. J. Olah³

¹Division of Metabolism, Department of Medicine, University Hospital (Kantonsspital) of Basle, Basle/Switzerland
²Department of Pathophysiology, University of Berne, Berne/Switzerland
³Department of Anatomy, University of Berne, Berne/Switzerland

Abstract

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Abstract

Eight patients with active Paget's disease of bone were treated with the diphosphonate EHDP for up to ten months. The drug was well tolerated, causing no toxic side effects. Bone turnover and bone remodelling were assessed before and on EHDP by combining the determination of serum alkaline phosphatase and urinary hydroxyproline excretion with complete metabolic balances, calcium kinetics and profile scanning on one hand and histomorphometry of paired bone biopsies on the other.

In all patients, EHDP led to a significant decrease of the biochemical and calcium kinetic parameters of bone turnover. Two degrees of response were seen: In "complete responders", i.e. subjects with a localized form of Paget's disease the abnormal radioactivity peak over the pagetic area disappeared, and histologic indices of bone resorption fell dramatically. Since parameters of bone degradation were more profoundly affected than parameters of bone formation, a more positive calcium balance was recorded on EHDP. In addition, the broadening of osteoid seams and a defective tetracycline labeling indicated impairment of mineralization in the pagetic bone of this patient group.

In "limited responders", a less marked influence of EHDP on metabolic and histologic parameters of bone turnover was recorded. Ca⁴⁷ activity profiles over the diseased area remained either unchanged or showed an only limited response. The osteoid seam width remained normal. Patients of this group suffered from a more severe, polyostotic type of Paget's disease.

In the sequence of events, urinary hydroxyproline started to decrease first, reaching a new plateau after two months of treatment. Serum alkaline phosphatase followed with a delay time of a further two months. After cessation of treatment in three subjects, both parameters remained normal in one patient for 20 months but tended to rise after eight and ten months respectively in the other two.

Thus, EHDP inhibits the excessive bone turnover in Paget's disease and may therefore constitute an effective treatment for this condition.

Key words

Paget's Disease of Bone - Diphosphonate - Calcium Balance - Calcium Kinetics - Histomorphometry

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References

1 Presented in part at the Seventh Annual Meeting of the European Society for Clinical Investigation, Rotterdam, April 1973.

2 Supported by Schweiz. Nationalfonds zur Forderung der wissenschaftlichen Forschung, Grants Nr. 3.104.69 and 3.804.72 (H.G.H.), 3.326.70 (H.F.) and 3.262.69 (A.J.O., R.K.S.)