Timing of Ibuprofen Use and Musculoskeletal Adaptations to Exercise Training in Older Adults

Catherine M Jankowski, Karen Shea, Daniel W Barry, Sunny A Linnebur, Pamela Wolfe, John Kittelson, Robert S Schwartz, Wendy M Kohrt, Catherine M Jankowski, Karen Shea, Daniel W Barry, Sunny A Linnebur, Pamela Wolfe, John Kittelson, Robert S Schwartz, Wendy M Kohrt

Abstract

Prostaglandins (PG) increase in bone in response to mechanical loading and stimulate bone formation. Inhibition of cyclooxygenase (COX), the enzyme responsible for PG synthesis, by non-steroidal anti-inflammatory drugs (NSAIDs) impairs the bone formation response to loading in animals when administered before, but not after, loading. The aim was to determine whether the timing of ibuprofen use (400 mg before versus after exercise sessions) is a significant determinant of the adaptive response of BMD to exercise training in older adults. We hypothesized that taking ibuprofen before exercise would attenuate the improvements in total hip and lumbar spine BMD in response to 36 weeks of training when compared with placebo or with ibuprofen use after exercise. Untrained women and men (N=189) aged 60 to 75 years were randomly assigned to 1 of 3 treatment arms: placebo before and after exercise (PP); ibuprofen before and placebo after exercise (IP); and placebo before and ibuprofen after exercise (PI). The difference between groups in the change in BMD was not significant when IP was compared with either PP (hip, -0.5% (-1.4, 0.4); spine, 0.1% (-0.9, 1.2)) or PI (hip, 0.3% (-0.6, 1.2); spine, 0.5% (-0.5, 1.5)). Ibuprofen use appeared to have more adverse effects on BMD in women than men. The study demonstrated that ibuprofen use did not significantly alter the BMD adaptations to exercise in older adults, but this finding should be interpreted cautiously. It had been expected that the inhibition of bone formation by ibuprofen would be as robust in men than women, but this did not appear to be the case and may have limited the power to detect the effects of ibuprofen. Further research is needed to understand whether NSAID use counteracts, in part, the beneficial effects of exercise on bone.

Keywords: Exercise training; bone mineral density; cyclooxygenase; nonsteroidal anti-inflammatory drugs; prostaglandins.

Figures

Fig. 1
Fig. 1
Recruitment, enrollment, and retention of study volunteers.
Fig. 2
Fig. 2
Relative changes in BMD, adjusted for baseline BMD, in response to 36 weeks of exercise training in older adults who took ibuprofen 400 mg before (ibuprofen/placebo) or after (placebo/ibuprofen) exercise sessions or placebo at both time points (placebo/placebo). The error bars represent SD.
Fig. 3
Fig. 3
Relative changes in BMD, adjusted for baseline BMD, in response to 36 weeks of exercise training in women (top panel) and men (bottom panel) who took ibuprofen 400 mg before (ibuprofen/placebo) or after (placebo/ibuprofen) exercise sessions or placebo at both time points (placebo/placebo). The error bars represent SD.

References

    1. Alam I., Warden S.J., Robling A.G., Turner C.H. Mechanotransduction in bone does not require a functional cyclooxygenase-2 (COX-2) gene. J. Bone Miner. Res. 2005;20:438–446.
    1. Bauer D.C., Orwoll E.S., Fox K.M., Vogt T.M., Lane N.E., Hochberg M.C., Stone K., Nevitt M.C. Aspirin and NSAID use in older women: effect on bone mineral density and fracture risk. Study of Osteoporotic Fractures Research Group. J. Bone Miner. Res. 1996;11:29–35.
    1. Benjamini Y., Hocberg Y. Controlling the false discovery rate: a new and powerful approach to multiple testing. J. R. Stat. Soc. Ser. B. 1995:1289–1300.
    1. Blackwell K.A., Raisz L.G., Pilbeam C.C. Prostaglandins in bone: bad cop, good cop? Trends Endocrinol. Metab. 2010;21:294–301.
    1. Capone M.L., Tacconelli S., Di Francesco L., Sacchetti A., Sciulli M.G., Patrignani P. Pharmacodynamic of cyclooxygenase inhibitors in humans. Prostaglandins Other Lipid Mediat. 2007;82:85–94.
    1. Carbone L.D., Tylavsky F.A., Cauley J.A., Harris T.B., Lang T.F., Bauer D.C., Barrow K.D., Kritchevsky S.B. Association between bone mineral density and the use of nonsteroidal anti-inflammatory drugs and aspirin: impact of cyclooxygenase selectivity. J. Bone Miner. Res. 2003;18:1795–1802.
    1. Cheng M.Z., Zaman G., Rawlinson S.C., Pitsillides A.A., Suswillo R.F., Lanyon L.E. Enhancement by sex hormones of the osteoregulatory effects of mechanical loading and prostaglandins in explants of rat ulnae. J. Bone Miner. Res. 1997;12:1424–1430.
    1. Chow J.W. Role of nitric oxide and prostaglandins in the bone formation response to mechanical loading. Exerc. Sport Sci. Rev. 2000;28:185–188.
    1. Chow J.W., Chambers T.J. Indomethacin has distinct early and late actions on bone formation induced by mechanical stimulation. Am. J. Physiol. 1994;267:E287–E292.
    1. Chow J.W., Fox S.W., Lean J.M., Chambers T.J. Role of nitric oxide and prostaglandins in mechanically induced bone formation. J. Bone Miner. Res. 1998;13:1039–1044.
    1. Davies N.M. Clinical pharmacokinetics of ibuprofen. The first 30 years. Clin. Pharmacokinet. 1998;34:101–154.
    1. Forwood M.R. Inducible cyclo-oxygenase (COX-2) mediates the induction of bone formation by mechanical loading in vivo. J. Bone Miner. Res. 1996;11:1688–1693.
    1. Gleeson M. Immune function in sport and exercise. J. Appl. Physiol. 2007;103:693–699. ((1985))
    1. Gorski T., Cadore E.L., Pinto S.S., da Silva E.M., Correa C.S., Beltrami F.G., Kruel L.F. Use of NSAIDs in triathletes: prevalence, level of awareness and reasons for use. Br. J. Sports Med. 2011;45:85–90.
    1. Holmes N., Cronholm P.F., Duffy A.J., III, Webner D. Nonsteroidal anti-inflammatory drug use in collegiate football players. Clin. J. Sport Med. 2013;23:283–286.
    1. Jankowski C.M., Gozansky W.S., Schwartz R.S., Dahl D.J., Kittelson J.M., Scott S.M., Van Pelt R.E., Kohrt W.M. Effects of dehydroepiandrosterone replacement therapy on bone mineral density in older adults: a randomized, controlled trial. J. Clin. Endocrinol. Metab. 2006;91:2986–2993.
    1. Ko F.C., Dragomir C., Plumb D.A., Goldring S.R., Wright T.M., Goldring M.B., van der Meulen M.C. In vivo cyclic compression causes cartilage degeneration and subchondral bone changes in mouse tibiae. Arthritis Rheum. 2013;65:1569–1578.
    1. Kohrt W.M., Barry D.W., Van Pelt R.E., Jankowski C.M., Wolfe P., Schwartz R.S. Timing of ibuprofen use and bone mineral density adaptations to exercise training. J. Bone Miner. Res. 2010;25:1415–1422.
    1. Kunnel J.G., Igarashi K., Gilbert J.L., Stern P.H. Bone anabolic responses to mechanical load in vitro involve COX-2 and constitutive NOS. Connect. Tissue Res. 2004;45:40–49.
    1. Li J., Burr D.B., Turner C.H. Suppression of prostaglandin synthesis with NS-398 has different effects on endocortical and periosteal bone formation induced by mechanical loading. Calcif. Tissue Int. 2002;70:320–329.
    1. Morton D.J., Barrett-Connor E., Schneider D.L. Nonsteroidal anti-inflammatory drugs and bone mineral density in older women: the Rancho Bernardo study. J. Bone Miner. Res. 1998;13:1924–1931.
    1. Poulet B., Hamilton R.W., Shefelbine S., Pitsillides A.A. Characterizing a novel and adjustable noninvasive murine joint loading model. Arthritis Rheum. 2011;63:137–147.
    1. Redlich K., Smolen J.S. Inflammatory bone loss: pathogenesis and therapeutic intervention. Nat. Rev. Drug Discov. 2012;11:234–250.
    1. Richards J.B., Joseph L., Schwartzman K., Kreiger N., Tenenhouse A., Goltzman D. The effect of cyclooxygenase-2 inhibitors on bone mineral density: results from the Canadian Multicentre Osteoporosis Study. Osteoporos. Int. 2006;17:1410–1419.
    1. Rodemann H.P., Goldberg A.L. Arachidonic acid, prostaglandin E2 and F2 alpha influence rates of protein turnover in skeletal and cardiac muscle. J. Biol. Chem. 1982;257:1632–1638.
    1. Sugiyama T., Meakin L.B., Galea G.L., Lanyon L.E., Price J.S. The cyclooxygenase-2 selective inhibitor NS-398 does not influence trabecular or cortical bone gain resulting from repeated mechanical loading in female mice. Osteoporos. Int. 2013;24:383–388.
    1. Thorsen K., Kristoffersson A.O., Lerner U.H., Lorentzon R.P. In situ microdialysis in bone tissue. Stimulation of prostaglandin E2 release by weight-bearing mechanical loading. J. Clin. Investig. 1996;98:2446–2449.
    1. Trappe T.A., Fluckey J.D., White F., Lambert C.P., Evans W.J. Skeletal muscle PGF(2)(alpha) and PGE(2) in response to eccentric resistance exercise: influence of ibuprofen acetaminophen. J. Clin. Endocrinol. Metab. 2001;86:5067–5070.
    1. Trappe T.A., White F., Lambert C.P., Cesar D., Hellerstein M., Evans W.J. Effect of ibuprofen and acetaminophen on postexercise muscle protein synthesis. Am. J. Physiol. 2002;282:E551–E556.
    1. Trappe T.A., Carroll C.C., Dickinson J.M., LeMoine J.K., Haus J.M., Sullivan B.E., Lee J.D., Jemiolo B., Weinheimer E.M., Hollon C.J. Influence of acetaminophen and ibuprofen on skeletal muscle adaptations to resistance exercise in older adults. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2011;300:R655–R662.
    1. Vestergaard P., Hermann P., Jensen J.E., Eiken P., Mosekilde L. Effects of paracetamol, non-steroidal anti-inflammatory drugs, acetylsalicylic acid, and opioids on bone mineral density and risk of fracture: results of the Danish Osteoporosis Prevention Study (DOPS) Osteoporos. Int. 2012;23:1255–1265.
    1. Warner D.C., Schnepf G., Barrett M.S., Dian D., Swigonski N.L. Prevalence, attitudes, and behaviors related to the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in student athletes. J. Adolesc. Health. 2002;30:150–153.
    1. Zaman G., Suswillo R.F., Cheng M.Z., Tavares I.A., Lanyon L.E. Early responses to dynamic strain change and prostaglandins in bone-derived cells in culture. J. Bone Miner. Res. 1997;12:769–777.
    1. Zhou Y., Boudreau D.M., Freedman A.N. Trends in the use of aspirin and nonsteroidal anti-inflammatory drugs in the general U.S. population. Pharmacoepidemiol. Drug Saf. 2013;23:43–50.

Source: PubMed

3
Subscribe