Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1991 Oct;88(4):1167–1172. doi: 10.1172/JCI115418

Decreased DNA synthesis by cultured osteoblastic cells in eugonadal osteoporotic men with defective bone formation.

P J Marie 1, M C de Vernejoul 1, D Connes 1, M Hott 1
PMCID: PMC295577  PMID: 1918371

Abstract

To determine the osteoblastic dysfunction that may be involved in the pathophysiology of osteoporosis in men we have compared histomorphometric indices of bone formation with in vitro characteristics of osteoblastic cells isolated from the trabecular bone surface in 23 untreated men with eugonadal osteoporosis. In most patients (n = 14), trabecular bone loss resulted from decreased bone formation evidenced by a lower than normal osteoblast surface, double tetracycline labeled surface, bone formation rate, and mean wall thickness. In these patients, DNA synthesis by cultured osteoblastic cells was altered. The peak of [3H]thymidine incorporation into DNA, the maximal DNA synthesis, and the area under the curve of cell proliferation were lower than the values in normal bone cells from age-matched controls. Parameters of bone cell growth were decreased in correlation with the extent of actively bone forming surfaces. By contrast, in patients (n = 9) with normal histomorphometric indices of bone formation, bone cell proliferation in vitro was not different from normal. Parameters of osteoblastic differentiation in vitro such as osteocalcin production and alkaline phosphatase activity were normal in the two groups of patients. This study shows that the trabecular bone loss resulting from defective bone formation in eugonadal osteoporotic men is associated with a lower than normal proliferative capacity of osteoblastic cells lining the trabecular bone surface.

Full text

PDF
1167

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bikle D. D., Genant H. K., Cann C., Recker R. R., Halloran B. P., Strewler G. J. Bone disease in alcohol abuse. Ann Intern Med. 1985 Jul;103(1):42–48. doi: 10.7326/0003-4819-103-1-42. [DOI] [PubMed] [Google Scholar]
  2. Clinical indications for bone mass measurements. A report from the Scientific Advisory Board of the National Osteoporosis Foundation. J Bone Miner Res. 1989 Nov;4 (Suppl 2):1–28. doi: 10.1002/jbmr.5650040803. [DOI] [PubMed] [Google Scholar]
  3. Crilly R. G., Delaquerrière-Richardson L. Current bone mass and body weight changes in alcoholic males. Calcif Tissue Int. 1990 Mar;46(3):169–172. doi: 10.1007/BF02555039. [DOI] [PubMed] [Google Scholar]
  4. Daniell H. W. Osteoporosis of the slender smoker. Vertebral compression fractures and loss of metacarpal cortex in relation to postmenopausal cigarette smoking and lack of obesity. Arch Intern Med. 1976 Mar;136(3):298–304. doi: 10.1001/archinte.136.3.298. [DOI] [PubMed] [Google Scholar]
  5. Diamond T., Stiel D., Lunzer M., Wilkinson M., Posen S. Ethanol reduces bone formation and may cause osteoporosis. Am J Med. 1989 Mar;86(3):282–288. doi: 10.1016/0002-9343(89)90297-0. [DOI] [PubMed] [Google Scholar]
  6. Farley J. R., Fitzsimmons R., Taylor A. K., Jorch U. M., Lau K. H. Direct effects of ethanol on bone resorption and formation in vitro. Arch Biochem Biophys. 1985 Apr;238(1):305–314. doi: 10.1016/0003-9861(85)90169-9. [DOI] [PubMed] [Google Scholar]
  7. Garcia-Carrasco M., Gruson M., de Vernejoul M. C., Denne M. A., Miravet L. Osteocalcin and bone morphometric parameters in adults without bone disease. Calcif Tissue Int. 1988 Jan;42(1):13–17. doi: 10.1007/BF02555833. [DOI] [PubMed] [Google Scholar]
  8. Jackson J. A., Kleerekoper M. Osteoporosis in men: diagnosis, pathophysiology, and prevention. Medicine (Baltimore) 1990 May;69(3):137–152. doi: 10.1097/00005792-199005000-00002. [DOI] [PubMed] [Google Scholar]
  9. Jackson J. A., Kleerekoper M., Parfitt A. M., Rao D. S., Villanueva A. R., Frame B. Bone histomorphometry in hypogonadal and eugonadal men with spinal osteoporosis. J Clin Endocrinol Metab. 1987 Jul;65(1):53–58. doi: 10.1210/jcem-65-1-53. [DOI] [PubMed] [Google Scholar]
  10. Kragstrup J., Melsen F., Mosekilde L. Thickness of bone formed at remodeling sites in normal human iliac trabecular bone: variations with age and sex. Metab Bone Dis Relat Res. 1983;5(1):17–21. doi: 10.1016/0221-8747(83)90046-2. [DOI] [PubMed] [Google Scholar]
  11. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  12. Lomri A., Marie P. J., Tran P. V., Hott M. Characterization of endosteal osteoblastic cells isolated from mouse caudal vertebrae. Bone. 1988;9(3):165–175. doi: 10.1016/8756-3282(88)90006-3. [DOI] [PubMed] [Google Scholar]
  13. Marie P. J., Lomri A., Sabbagh A., Basle M. Culture and behavior of osteoblastic cells isolated from normal trabecular bone surfaces. In Vitro Cell Dev Biol. 1989 Apr;25(4):373–380. doi: 10.1007/BF02624601. [DOI] [PubMed] [Google Scholar]
  14. Marie P. J., Lomri A., de Vernejoul M. C., Morieux C., Graulet A. M., Guéris J., Llach F. Relationships between histomorphometric features of bone formation and bone cell characteristics in vitro in renal osteodystrophy. J Clin Endocrinol Metab. 1989 Dec;69(6):1166–1173. doi: 10.1210/jcem-69-6-1166. [DOI] [PubMed] [Google Scholar]
  15. Marie P. J., Sabbagh A., de Vernejoul M. C., Lomri A. Osteocalcin and deoxyribonucleic acid synthesis in vitro and histomorphometric indices of bone formation in postmenopausal osteoporosis. J Clin Endocrinol Metab. 1989 Aug;69(2):272–279. doi: 10.1210/jcem-69-2-272. [DOI] [PubMed] [Google Scholar]
  16. Orwoll E. S., Meier D. E. Alterations in calcium, vitamin D, and parathyroid hormone physiology in normal men with aging: relationship to the development of senile osteopenia. J Clin Endocrinol Metab. 1986 Dec;63(6):1262–1269. doi: 10.1210/jcem-63-6-1262. [DOI] [PubMed] [Google Scholar]
  17. Parfitt A. M., Drezner M. K., Glorieux F. H., Kanis J. A., Malluche H., Meunier P. J., Ott S. M., Recker R. R. Bone histomorphometry: standardization of nomenclature, symbols, and units. Report of the ASBMR Histomorphometry Nomenclature Committee. J Bone Miner Res. 1987 Dec;2(6):595–610. doi: 10.1002/jbmr.5650020617. [DOI] [PubMed] [Google Scholar]
  18. Parfitt A. M., Mathews C. H., Villanueva A. R., Kleerekoper M., Frame B., Rao D. S. Relationships between surface, volume, and thickness of iliac trabecular bone in aging and in osteoporosis. Implications for the microanatomic and cellular mechanisms of bone loss. J Clin Invest. 1983 Oct;72(4):1396–1409. doi: 10.1172/JCI111096. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Pocock N. A., Eisman J. A., Kelly P. J., Sambrook P. N., Yeates M. G. Effects of tobacco use on axial and appendicular bone mineral density. Bone. 1989;10(5):329–331. doi: 10.1016/8756-3282(89)90128-2. [DOI] [PubMed] [Google Scholar]
  20. Pocock N. A., Eisman J. A., Yeates M. G., Sambrook P. N., Eberl S. Physical fitness is a major determinant of femoral neck and lumbar spine bone mineral density. J Clin Invest. 1986 Sep;78(3):618–621. doi: 10.1172/JCI112618. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Riggs B. L., Wahner H. W., Dunn W. L., Mazess R. B., Offord K. P., Melton L. J., 3rd Differential changes in bone mineral density of the appendicular and axial skeleton with aging: relationship to spinal osteoporosis. J Clin Invest. 1981 Feb;67(2):328–335. doi: 10.1172/JCI110039. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. SAVILLE P. D. CHANGES IN BONE MASS WITH AGE AND ALCOHOLISM. J Bone Joint Surg Am. 1965 Apr;47:492–499. [PubMed] [Google Scholar]
  23. Seeman E., Melton L. J., 3rd, O'Fallon W. M., Riggs B. L. Risk factors for spinal osteoporosis in men. Am J Med. 1983 Dec;75(6):977–983. doi: 10.1016/0002-9343(83)90878-1. [DOI] [PubMed] [Google Scholar]
  24. Sparrow D., Beausoleil N. I., Garvey A. J., Rosner B., Silbert J. E. The influence of cigarette smoking and age on bone loss in men. Arch Environ Health. 1982 Jul-Aug;37(4):246–249. doi: 10.1080/00039896.1982.10667572. [DOI] [PubMed] [Google Scholar]
  25. Williams A. R., Weiss N. S., Ure C. L., Ballard J., Daling J. R. Effect of weight, smoking, and estrogen use on the risk of hip and forearm fractures in postmenopausal women. Obstet Gynecol. 1982 Dec;60(6):695–699. [PubMed] [Google Scholar]
  26. de Vernejoul M. C., Bielakoff J., Herve M., Gueris J., Hott M., Modrowski D., Kuntz D., Miravet L., Ryckewaert A. Evidence for defective osteoblastic function. A role for alcohol and tobacco consumption in osteoporosis in middle-aged men. Clin Orthop Relat Res. 1983 Oct;(179):107–115. [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES