Summary
Localized osteoclastic bone resorption plays a significant role in the pathogenesis of several diseases of the middle ear as well as orthodontic tooth movement and long bone remodeling. The mechanisms of control of localized bone loss and systemic bone resorption may be different but both may be mediated by a final common pathway which includes prostaglandins. Prostaglandins seem to have a predominantly stimulatory effect on bone resorption, although the exact mechanism is poorly understood. Ibuprofen, a nonsteroidal antiinflammatory drug, is known to inhibit the synthesis of prostaglandins. It is likely that ibuprofen, through its inhibition of prostaglandin synthesis, would decrease the localized osteoclastic bone resorption in a previously described animal model system. Mongolian gerbils were divided into three groups: low dose ibuprofen (10 mg/kg per day), high dose ibuprofen (30 mg/kg per day), and a control group. Following surgical implantation of catheters to the right bullae of each gerbil, pressure was applied for 8 days, stimulating osteoclastic bone resorption. After killing the animals and histomorphometric analysis of the bullae from each, comparisons were made between each group using osteoclast surface (percentage of bone area covered by osteoclasts), osteoclast number (number of osteoclasts/mm bone length), and osteoclast profile area (in μm2). Significantly lower osteoclast surface (Oc. S/BS) was found in pressurized bullae from both treatment groups when compared with pressurized bullae from controls (P<0.05) and significantly lower osteoclast number (N.Oc/T.L) in pressurized bullae from both treatment groups when compared with pressurized bullae from controls (P<0.05). These differences were found to be dose-dependent. No significant differences in individual osteoclast profile area were found in either treatment group when compared with controls.
Similar content being viewed by others
References
Chole RA (1988) The role of osteoclasts in diseases of the middle ear: chronic otitis media, cholesteatoma and otosclerosis. Ann Otol Rhinol Laryngol 97:661–666
Davis GL (1987) Pathology of otosclerosis: a review. Am J Otolaryngol 8:273–281
Mundy GR, Roodman GD (1987) Osteoclast ontogeny and function. In: Peck WA (ed) Bone and mineral research. Elsevier Science Publishers. Amsterdam, pp 246–250
Davidovitch Z, Shanfield JL, Lally E (1982) Prostaglandin F2α is associated with alveolar bone cells: immunohistochemical evidence utilizing monoclonal antibodies. In: Dixon AD, Sarnat BG (eds) Factors and mechanisms influencing bone growth. Alan Liss, New York, pp 125–134
Jung TTK, Juhn SK, Gerrard JM (1982) Identification of prostaglandins and other arachidonic acid metabolites in experimental otitis media. Prostaglandins Leukotrienes Med 8:249
Brenner DE, Harvey HA, Lipton A, Demers L (1982) A study of prostaglandin E2, parathormone and response to indomethacin in patients with hypercalcemia and malignancy. Cancer 49:556–561
Tashjian AH, Voelkel EF, Levine L, Goldhaber P (1972) Evidence that the bone resorption stimulating factor produced by mouse fibrosarcoma cells is prostaglandin E2: a new model for the hypercalcemia of cancer. J Exp Med 136:1329–1343
Adachi K, Chole RA, Yee J (1990) Indomethacin inhibition of osteoclastic bone resorption in vivo. Ann Otol Rhinol Laryngol (submitted)
Nuki G (1983) Non-steroidal analgesic and anti-inflammatory agents. Br Med J 287:39
Chole RA, Chan DE (1989) Rapid induction of localized bone resorption in the auditory bulla of the mongolian gerbil,Meriones unguiculatus, by increased air pressure. Calcif Tissue Int 45:318–323
Wolfman DE, Chole RA (1986) Osteoclast stimulation by positive middle-ear pressure. Arch Otolaryngol 112:1037–1042
Owen SG, Roberts MS, Friesen WT (1987) Rapid high-performance liquid chromatographic assay for the simultaneous analysis of non-steroidal anti-inflammatory drugs in plasma. J Chromatogr 416:293–300
Anderson D (1988) Pyschostats v. 4.5. Allegheny College, Meadville, Pennsylvania
Voelkel EF, Tashjian AH Jr., Franklin R, Wasserman E, Levine L (1975) Hypercalcemia and tumor prostaglandins: the VX2 carcinoma model in the rabbit. Metabolism 24:973–986
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
Tashjian AH, Voelkel EF, Goldhaber P, Levine L (1974) Prostaglandins, calcium metabolism, and cancer. Fed Proc 33:81–86
Franklin RB, Tashjian AH Jr (1975) Intravenous infusion of PGE2 raises calcium concentration in rats. Endocrinology 97:240–243
Yamaski K, Shibata Y, Imai S, Tani Y, Shibasaki Y, Fukuhara T (1984) Clinical application of prostaglandin E1 (PGE1) upon orthodontic tooth movement. Am J Orthod 85:508–518
Chumbly AB, Tuncay OC (1986) The effect of indomethacin on the rate of orthodontic tooth movement. Am J Orthod 89:312–314
Jung TTK, Juhn SK, Michael AF (1983) Localization of prostaglandin-forming cyclooxygenase in the middle ear and external canal tissue. Oto H&N Surg 91:187–192
Chambers TJ, Ali NN (1983) Inhibition of osteoclastic motility by prostaglandins I2, E1, E2, and 6-oxyE1. J Pathol 139:383–398
Neuman SD, Raisz LG (1984) Effects of the prostacyclin products, 6-Keto prostaglandin E1 and 6-Keto prostaglandin F1α on bone resorption in vitro. Prostaglandins Leukotrienes Med 15:103–108
Dietrich JW, Goodson JM, Raisz LG (1975) Stimulation of bone resorption by various prostaglandins in organ culture. Prostaglandins 10:231–238
Klein DC, Raisz LG (1970) Prostaglandins: stimulation of bone resorption in tissue culture. Endocrinology 86:1436
Tashjian AH, Voelkel EF, Lazzaro M, Goad D, Bosma T, Levine L (1987) Tumor necrosis factor-α (cachectin) stimulates bone resorption in mouse calvaria via a prostaglandin mediated mechanism. Endocrinology 120:2029–2036
Robinson DR, Tashjian AH Jr, Levine L (1975) Prostaglandin-stimulated bone resorption by rheumatoid synovia. J Clin Invest 56:1181–1188
Williams RC, Jeffcoat MK, Howell TH, Ready MS, Johnson HG, Hall CM, Goldhaber P (1988) Ibuprofen: an inhibitor of alveolar bone resorption in beagles. J Periodont Res 23:225–229
Jung TTK (1988) Prostaglandins, leukotrienes, and other arachidonic acid metabolites in the pathogenesis of otitis media. Laryngoscope 98:980–993
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Jungkeit, M.C., Chole, R.A. Ibuprofen inhibits localized bone resorption in the middle ear. Calcif Tissue Int 48, 267–271 (1991). https://doi.org/10.1007/BF02556378
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF02556378