Summary
The present study deals with qualitative und quantitative analysis of osteoclastic bone resorption in metastatic bone disease. 267 cases were examined histomorphologically and divided into three developmental stages. In the first ‘phase of early appearance’ no bone resorption takes place. The stimulation of osteoclastic resorption in the surroundings of tumour tissue is typical in the second ‘phase of interaction’. Pressure atrophy, aseptic necrosis and osteolysis by the tumour cells themselves are other mechanisms of bone destruction in the last ‘phase of carcinomatosis’. Because osteoclasts are exclusively responsible for the loss of bone tissue in the ‘phase of interaction’, this stage is suited for precise quantitative analysis of osteoclastic resorption. 24 pure osteolytic secondary bone tumours of various primary lesions were examined histomorphometrically. The numerical values were compared with each other and with standard values of healthy individuals. In contrast with normal bone tissue the fractional resorption surfaces und osteoclast indices increase in metastases. Activated osteoclasts are larger and have more nuclei. The numbers of osteoclast index and nuclei per osteoclast are significantly higher in renal than in breast carcinoma. Osteoclasts can be activated in distances of more than 500 µm from tumour tissue. The mean stimulation distance in metastasis from squamous cell carcinoma is markedly higher than in secondary bone tumours of breast carcinoma. Several osteoclast activating substances and divers mechanisms of stimulation might be responsible for different numerical values of morphometric parameters in metastases from various primary malignancies.
Similar content being viewed by others
References
Baron R (1977) Importance of intermediate phase between resorption and formation in the measurement and unterstanding of the bone remodeling sequence. In: Meunier PJ (ed) Bone histomorphometry, second international workshop. Toulouse, France: Société de la Nouvelle Imprimerie Fournie, pp 179–183
Bennet A, Simpson JS, Mc Donald AM, Stamford IF (1975) Breast cancer, prostaglandins and bone metastases. Lancet 31:1218–1220
Binstock ML, Mundy GR (1980) Effect of calcitonin and glucocorticoids in combination on hypercalcemia of malignancy. Ann Int Med 93:269–272
Bonucci E (1981) New knowledge on the origin, function and fate of osteoclasts. Clin Orthop 158:252–269
Bringhurst FR, Vorner V, Segre GV (1982) Cancer associated hypercalcemia: Characterization of a new bone resorbing factor. Clin Res 30/2:386A
Caro JF, Beserab A, Flymn JT (1979) Prostaglandin E and hypercalcemia in breast carcinoma: only a tumour marker? Am J Med 66:337–341
Chambers TJ (1980) The cellular basis of bone resorption. Clinical Orthop Rel Res 151:283–293
Chambers TJ, Dunn CJ (1982) The effect of parathroid hormone, 1,25 dihydroxycholecalciferol and prostaglandins on the cytoplasmatic activity of isolated osteoclasts. J Path 137:193–203
Chambers TJ, Path MRC (1980) The cellular basis of bone resorption. Clin Orthop Rel Res 151:283–293
Cramer SF, Fried L, Carter KJ (1981) The cellular basis of metastatic bone disease in patients with lung cancer. Cancer 48:2649–4660
Delling G (1972) Über eine vereinfachte Methacrylateinbettung für unentkalkte Knochenschnitte. Beitr Pathol 145:100–105
Delling G (1975) Endocrine Osteopathien. Morphologie, Histomorphometrie, Differentialdiagnose. Veröffentlichungen aus der Pathologie. Heft 98. Stuttgart: Gustav Fischer Verlag
Delling G (1979) Morphometrie des Knochengewebes. Dtsch Ges Innere Med 229–239
Delling G, Luehmann H, Baron R, Mathews CHE, Olah A (1981) Investigation of intra-reader retroducibility. In: Jee WSS, Parfitt M (eds). Bone Histomorphometry, Third International Workshop. Paris: Société Nouvelle de Publications Médicales et Deutaires. 419–427
De Maria D, Mandolini G, Falchi AM, Balli M (1979) La calcitonina nel Trattamento di Pazienti con Metastasi ossee da carcinoma mammario: Esperienze chliniche in calcitonina: nuove asquisizioni e prospettive. In: De Bastiani G, Pecile A, Pietrograde V, Sirtori C (eds) Fondazione Carlo Erba, Milano
Eilon G, Mundy GR (1979) Increase in cyclic AMP in human brest cancer cells causes release of hydrolytic encymes and bone resorbing activity. Presented at first annual meeting of the American Society for Bone and Mineral Research. Anaheim, California
Elomaa I, Blomquist C, Porkka L (1984) Supportive clodrante therapy for bone metastasis, a follow-up period. Calcif Tissue [Suppl] 36/2:28
Fleisch H, Felix R (1979) Diphosphonates. Calcif Tissue Res 27:91–94
Frost HM (1963) Bone remodeling dynamics. Thomas, Springfield, Illinois
Frost HM (1977) A method of analysis of trabecular bone dynamics. In: Meunier PJ, Bone histomorphometry. Second International Workshop, Toulouse, France: Société de la Nouvelle Imprimerie Fournie, pp 445–476
Galasko CSB, Bennet A (1976) Relationship of bone destruction in skeletal metastasis to osteoclast activation and protaglandins. Nature 263:508–510
Galasko CSB, Samuel AW, Rushton S, Lacey E (1980) The effect of prostaglandin synthesis inhibitors and diphosphonates on tumour induced osteolysis. Br J Surg 67:493–496
Galasko CSB (1981) The development of skeletal metastases. In: Weiss LW, Gilbert HA (eds) Bone metastasis. Hall GK, Medical Publ, Boston, pp 49–63
Gordan GS, Roof BS, Halden A (1973) Skeletal effects of cancer and their management. In: Holland JF, Frei E (eds) Lea and Febinger. Cancer Medicine, Philadelphia, pp 1073–1083
Hasling C, Charles P, Mosekilde L (1984) Intravenous EHDP for treatment of hypercalcemia of malignancy. Calcif Tissue [Suppl 36] 2:28
Jee WSS, Kimmel DB (1977) Bone cell origin at the endosteal surface. In: Meunier PJ. Bone Histomorphometry. Second International Workshop. Toulouse, France: Societe de la Nouvelle Imprimerie Fournie, pp 113–131
Jung A, Mermillod B, Barras C, Baud M, Courvoisier (1981) Inhibition by two diphosphonates for treating malignant hypercalcemia. Cancer 48:1922–1925
Jung A (1983) Inhibition of tumour induced osteolysis. In: Stoll BA, Parbhoo S (eds) Bone Metastasis: Monitoring and Treatment. Raven Press, New York, pp 47–57
Koeffler HP, Mundy GR, Golde DW, Cline MJ (1978) Production of tumour resorbing activity in poorly differentiated monocytic malignancy. Cancer 41:2438
Kulenkampff H-A, Delling G (1984) Die Stimulation der osteoclastaeren Osteolyse bei Knochenmetastasen- eine quantitative Untersuchung. Verh Dtsch Ges Pathol 68:518
Merz WA (1967) Die Streckenmessung an gerichteten Strukturen im Mikroskop und ihre Anwendung zur Bestimmung von Oberflächen-Volumen-Relationen im Knochengewebe. Mikroskopie 22:132–142
Milch RA, Changus GW (1956) Response of bone to tumour invasion. Cancer 9:341–351
Mundy GR, Luben RA, Raisz LG, Oppenheim JJ, Buell DN (1974) Bone resorbing activity in supernatants from lymphoid cell lines. N Engl J Med 290:867–871
Mundy GR, Raisz LG, Cooper RA, Schechter GP, Salmon SE (1974) Evidence for the secretion of an osteoclast stimulating factor in myeloma. N Engl J Med 291:1041–1046
Mundy GR, Raisz LG (1977) Big and little forms of osteoclast activating factor. J Clin Invest 60:122–128
Mundy GR, Ibbotson KJ, D'Souza SM (1984) Bone and cancer. Calcif Tiss (Sup) 36/2:25
Omenn GS, Roth SI, Baker WH (1969) Hyperparathyroidism associated with malignant tumour of non-parathyroid origin. Cancer 24:1004–1012
Perlia CP, Gubisch NJ, Wolter J, Edelberg D, Deterich MM, Taylor III SG (1970) Mithramycin treatment of hypercalcemia. Cancer 25:389–394
Powles TJ, Dowsett M, Easty GC, Easty DM, Neville AM (1976) Breast cancer osteolysis bone metastases and anti-osteolytic effect of aspirin. Lancet 1:608–610
Raisz LG, Luben RA, Mundy GR, Dietrich JW, Horton JE, Trummel CL (1975) Effect of osteoclast activating factor from human leucocytes on bone metabolism. J Clin Invest 56:408–413
Raisz LG, Yahing CH, Bock RS, Bower BF (1979) Comparison of commercially available parathyroid hormone immunassys in the differential diagnosis of hypercalcemia due to primary hyperparathyreoidism of malignancy. Ann Int Med 91:739–740
Rodan GA, Martin TJ (1981) Role of osteoblasts in humoral control of bone resorption- a hypothesis. Calcif Tissue Int 33:349–351
Scherwood LM, O'Riordan JLM, Aurbach GM, Potts FT jr (1967) Production of parathyroid hormone by non parathyroid tumours. J Clin Endocrinol 27:140–146
Seyberth HW, Segre GV, Morgan JL, Sweetman BJ, Potts JT jr, Oates JA (1975) Prostaglandins as mediators of hypercalcemia associated with certain types of cancer. N Engl J Med 293:1278–1283
Simpson El, Mundy GR, D'Souza SM, Ibbotson KJ, Bockman R, Jacobs JW (1983) Absence of parathyroid hormone messenger RNA in nonparathyroid tumours associated with hypercalcemia. N Engl J Med 309/6:325–330
Stamp TCB, Child JA, Walker PG (1975) Treatment of osteolytic myolysis with mithramycin. Lancet 29:719–722
Tashjian AH (1978) Role of prostaglandins in the production of hypercalcemia by tumours. Cancer Res 38:4138–4143
Tashjian AH jr, Levine L (1978) Epidermal growth factor stimulates prostaglandin production and bone resorption in cultured mouse calvaria. Biochem Biophys Res Commun 85:966–975
Todaro GJ, Fryling C, De Larco JE (1980) Transforming growth factors produced by certain human tumour cells, polypeptides that interact with epidermal growth factor receptors. Proc Natl Acad Sci (USA) 77:5258–5262
Trump DL (1983) Mechanisms of bone destruction by cancer. In: Stoll BA, Parbhoo S (eds) Bone Metastasis: Monitoring and Treatment. Raven Press, New York, pp 39–46
Voekel EF, Tashjian AH jr, Franklin R, Wasserman E, Levine L (1975) Hypercalcemia and tumour prostaglandins: The VX-2 carcinoma model in rabbit. Metabolism 24:937–986
Author information
Authors and Affiliations
Additional information
Dedicated to Prof. Dr. G. Seifert on the occasion of his 65th birthday
Rights and permissions
About this article
Cite this article
Kulenkampff, H.A., Dreyer, T., Kersjes, W. et al. Histomorphometric analysis of osteoclastic bone resorption in metastatic bone disease from various primary malignomas. Vichows Archiv A Pathol Anat 409, 817–828 (1986). https://doi.org/10.1007/BF00710766
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00710766