Advertisement

The Biochemistry of Paget’s Disease

  • Stephen M. Krane

Abstract

The characteristic biological abnormalities of Paget’s disease reflect the disordered bone remodeling. It is likely that the initial event in this disease is a focal, intense resorption of existing bone associated with the presence of abnormal large osteoclasts. At the point where the lesions are usually recognized, increased production of woven and lamellar bone is evident, as well as replacement of normal fatty and hematopoietic marrow with a loose fibrous stroma. Coupling of bone formation with bone resorption is evidenced by quantitative histomorphometry and can be confirmed by parallel charges in serum alkaline phosphatase levels and urinary hydroxyproline excretion, as well as by radiocalcium kinetics and measurements of other indexes of matrix protein synthesis and degradation. Although it has been assumed that the formation of pagetic bone is a coupled response to increased resorption, it should be emphasized that all pagetic bone is abnormal. The osteoblastic rate is high, the osteoblastic surface is increased, and the osteoblasts themselves are also probably not normal. The increase in osteoblast function could somehow result from contact of cell membranes of osteoclasts and osteoblasts or stromal cells or through release of some product of osteoclasts. Many of the remodeling events in Paget’s disease have been interpreted as consistent with an increased “birth rate” of all of the bone cell populations.1–6

Keywords

Bone Collagen Collagen Turnover Noncollagenous Protein Serum Alkaline Phosphatase Level Pagetic Bone 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Nagant de Deuxchaisnes C, Krane SM: Paget’s disease of bone: Clinical and metabolic observations. Medicine 1964;43(3)233–266.Google Scholar
  2. 2.
    Paget’s disease of bone. Editorial. Calcif Tissue Int 1986; 38: 309–317.CrossRefGoogle Scholar
  3. 3.
    Singer FR, Krane SM: Paget’s disease of bone, in Avioli LV, Krane SM (eds): Metabolic Bone and Disease and Clinically Related Disorders. Philadelphia, WB Saunders Co, 1990, pp 546–615.Google Scholar
  4. 4.
    Bijovet OLM, Vellenga CJLR, Harinck HIJ: Paget’s disease of bones: Assessment, therapy, and secondary prevention, in Kleerekoper M, Krane SM (eds): Clinical Disorders of Bone and Mineral Metabolism. New York, Mary Ann Liebert, 1989, pp 525–542.Google Scholar
  5. 5.
    Krane SM: Skeletal metabolism in Paget’s disease of bone. Arthritis Rheum 1980; 23: 1087–1094.PubMedCrossRefGoogle Scholar
  6. 6.
    Krane SM, Simon LS: Metabolic consequences of bone turnover in Paget’s disease of bone. Clin Orthop 1987; 217: 26–36.PubMedGoogle Scholar
  7. 7.
    Krane SM, Brownell GL, Stanbury JB, Corrigan H: The effect of thyroid disease on calcium metabolism in man. J Clin Invest 1956; 35: 874–887.PubMedCrossRefGoogle Scholar
  8. 8.
    Termine JD: Non-collagen proteins in bone, in Everud D, Harnett S (eds): Cell and Molecular Biology of Vertebrate Hard Tissues. Chichester, England, Wiley, 1988, pp 178–202.Google Scholar
  9. 9.
    Ramirez F, De Wet W: Molecular biology of the human fibrillar collagen genes. Ann NY Acad Sci 1988; 543: 109–116.PubMedCrossRefGoogle Scholar
  10. 10.
    Pinneil SR, Fox R, Krane SM: Human collagens: Differences in glycosylated hydroxylysines in skin and bone. Biochim Biophys Acta 1971, 229: 119–122.Google Scholar
  11. 11.
    Eyre DR: Collagen stability through covalent crosslinking. Adv Meat Res 1987; 4: 69–85.Google Scholar
  12. 12.
    Krane SM, Munoz AJ, Harris ED Jr: Urinary polypeptides related to collagen synthesis. J Clin Invest 1970; 49: 716–729.PubMedCrossRefGoogle Scholar
  13. 13.
    Haddad JG, Couranz S, Avioli LV: Nondialyzable urinary hydroxyproline as an index of bone collagen formation. J Clin Endocrinol Metab 1970; 30: 282–287.PubMedCrossRefGoogle Scholar
  14. 14.
    Epstein S: Serum and urinary markers of bone remodeling: Assessment of bone turnover. EndocrRev 1988; 9: 437–449.PubMedCrossRefGoogle Scholar
  15. 15.
    Coulton LA, Preston CJ, Couch M, Kanis JA: An evaluation of serum osteocalcin in Paget’s disease of bone and its response to diphosphonate treatment. Arthritis Rheum 1988; 31: 1142–1147.PubMedCrossRefGoogle Scholar
  16. 16.
    Papapoulos SE, Frolich M, Mudde AH, et al: Serum osteocalcin in Paget’s disease of bone: Basal concentrations and response to bisphosphonate treatment. J Clin Endocrinol Metab 1987; 65: 89–94.PubMedCrossRefGoogle Scholar
  17. 17.
    Taylor AK, Linkhart SG, Mohan S, et al: Presence of a unique fragment of osteocalcin in serum and urine of Paget’s disease patients: Possible marker for the disease. J Bone Mineral Res 1989; 4 (suppl 1): S198.Google Scholar
  18. 18.
    Askenasi R, De Backer M, Devos A: The origin of urinary hydroxylysyl glycosides in Paget’s disease of bone and in primary hyperparathyroidism. Calcif Tissue Res 1976; 22: 35–40.PubMedCrossRefGoogle Scholar
  19. 19.
    Krane SM, Kantrowitz FG, Byrne M, et al: Urinary excretion of hydroxylysine and its glycosides as an index of collagen degradation. J Clin Invest 1977; 59: 819–827.PubMedCrossRefGoogle Scholar
  20. 20.
    Szymanowicz A: Polymorphism of urinary 4-hydroxyproline-containing polypeptides. J Chromatogr 1981; 225: 55–63.PubMedCrossRefGoogle Scholar
  21. 21.
    Sherr CJ, Goldberg B: Antibodies to a precursor of human collagen. Science 1973; 180: 1190–1192.PubMedCrossRefGoogle Scholar
  22. 22.
    Taubman MB, Goldberg B, Sherr CJ: Radioimmunoassay for human procollagen. Science 1974; 186: 1115–1117.PubMedCrossRefGoogle Scholar
  23. 23.
    Taubman MB, Kammerman S, Goldberg B: Radioimmunoassay of procollagen in serum of patients with Paget’s disease of bone. Proc Soc Exp Biol Med 1976; 152: 284–287.PubMedGoogle Scholar
  24. 24.
    Simon LS, Krane SM, Wortman PD, et al: Serum levels of type I and III procollagen fragments in Paget’s disease of bone. J Clin Endocrinol Metab 1984; 58: 110–120.PubMedCrossRefGoogle Scholar
  25. 25.
    Robins SP, Stewart P, Astbury C, Bird HA: Measurement of the cross linking compound, pryidinoline, in urine as an index of collagen degradation in joint disease. Ann Rheum Dis 1986; 45: 969–973.PubMedCrossRefGoogle Scholar
  26. 26.
    Eyre D, Ericsson L, Simon L, Krane S: Identification of urinary peptides derived from cross-linking sites in bone collagen in Paget’s disease. J Bone Mineral Res 1988; 3 (suppl): S210.Google Scholar
  27. 27.
    Robins SP, Duncan A, Reid DM, Paterson CR: Urinary hydroxy-pyridinium crosslinks of collagen as markers of resorption in a range of metabolic bone diseases. J Bone Min Res 1989; 4 (suppl 1): S397.Google Scholar

Copyright information

© Elsevier Science Publishing Co., Inc. 1991

Authors and Affiliations

  • Stephen M. Krane

There are no affiliations available

Personalised recommendations