In a 6-year cohort study of 751 community-dwelling elderly Japanese women, we found that C-reactive protein (CRP) is a significant predictor of osteoporotic fracture in elderly Asian women, who have significantly lower CRP levels than Caucasians. Mechanisms explaining such an association should be further studied.
While CRP, a systemic inflammation marker, is thought to be associated with osteoporosis, evidence supporting this claim has been limited. We aimed to assess the association between CRP levels and incident osteoporotic fracture in elderly women.
We conducted a cohort study with a follow-up period of 6 years. The study included 751 Japanese women aged 69 years or older. We measured serum high-sensitivity CRP (hs-CRP) levels as a major predictor. Covariates included age, body mass index, forearm bone mineral density, calcium intake, serum 25-hydroxyvitamin D, postural sway, osteoporosis medication, and physical activity. The primary outcome was incident limb and vertebral fractures. The Cox proportional hazards model was used to calculate the hazard ratio (HR) of fracture.
Median hs-CRP values in study participants were 0.16 mg/L in the lowest tertile, 0.36 mg/L in the medium tertile, and 1.14 mg/L in the highest tertile. The hs-CRP values in these women were substantially lower than in their Caucasian counterparts. Limb or vertebral fractures occurred in 50 subjects during 4,250 person-years. Low CRP levels were associated with low incidence of limb or vertebral fractures (P for trend = 0.035). The adjusted HRs of fracture for the medium and highest quartiles of hs-CRP levels, compared to the lowest quartile, were 2.22 (95% CI, 1.02–4.84) and 2.40 (95% CI, 1.10–5.24), respectively.
CRP is a significant predictor of osteoporotic fracture in elderly Asian women who have substantially lower CRP levels than Caucasians. Mechanisms explaining such an association should be further studied.
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Cauley JA, Danielson ME, Boudreau RM, Forrest KY, Zmuda JM, Pahor M, Tylavsky FA, Cummings SR, Harris TB, Newman AB, for the Health ABC Study (2007) Inflammatory markers and incident fracture risk in older men and women: the Health Aging and Body Composition Study. J Bone Miner Res 22:1088–1095
Danesh J, Wheeler JG, Hirschfield GM, Eda S, Eiriksdottir G, Rumley A, Lowe GD, Pepys MB, Gudnason V (2004) C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. N Engl J Med 350:1387–1397
Kritchevsky SB, Cesari M, Pahor M (2005) Inflammatory markers and cardiovascular health in older adults. Cardiovasc Res 66:265–275
Kuo HK, Yen CJ, Chang CH, Kuo CK, Chen JH, Sorond F (2005) Relation of C-reactive protein to stroke, cognitive disorders, and depression in the general population: systematic review and meta-analysis. Lancet Neurol 4:371–380
Brinkley TE, Leng X, Miller ME, Kitzman DW, Pahor M, Berry MJ, Marsh AP, Kritchevsky SB, Nicklas BJ (2009) Chronic inflammation is associated with low physical function in older adults across multiple comorbidities. J Gerontol A Biol Sci Med Sci 64:455–461
Clowes JA, Riggs BL, Khosla S (2005) The role of the immune system in the pathophysiology of osteoporosis. Immunol Rev 208:207–227
Pasco JA, Kotowicz MA, Henry MJ, Nicholson GC, Spilsbury HJ, Box JD, Schneider HG (2006) High-sensitivity C-reactive protein and fracture risk in elderly women. JAMA 296:1353–1355
Schett G, Kiechl S, Weger S, Pederiva A, Mayr A, Petrangeli M, Oberhollenzer F, Lorenzini R, Redlich K, Axmann R, Zwerina J, Willeit J (2006) High-sensitivity C-reactive protein and risk of nontraumatic fractures in the Bruneck study. Arch Intern Med 166:2495–2501
Nakamura K, Saito T, Oyama M, Oshiki R, Kobayashi R, Nishiwaki T, Nashimoto M, Tsuchiya Y (2010) Vitamin D sufficiency is associated with low incidence of limb and vertebral fractures in community-dwelling elderly Japanese women: the Muramatsu Study. Osteoporos Int (in press)
Nakamura K, Saito T, Nishiwaki T, Ueno K, Nashimoto M, Okuda Y, Tsuchiya Y, Oshiki R, Muto K, Yamamoto M (2006) Correlations between bone mineral density and demographic, lifestyle, and biochemical parameters in community dwelling Japanese women 69 years of age and over. Osteoporos Int 17:1202–1207
Nakamura K, Oshiki R, Hatakeyama K, Nishiwaki T, Ueno K, Nashimoto M, Saito T, Tsuchiya Y, Okuda Y, Yamamoto M (2006) Vitamin D status, postural sway, and the incidence of falls in elderly community-dwelling Japanese women. Arch Osteoporos 1:21–27
Orimo H, Sugioka Y, Fukunaga M, Muto Y, Hotokebuchi T, Gorai I, Nakamura T, Kushida K, Tanaka H, Ikai T, Oh-hashi Y (1998) Diagnostic criteria of primary osteoporosis. J Bone Mineral Metab 16:139–150
Arima H, Kubo M, Yonemoto K, Doi Y, Ninomiya T, Tanizaki Y, Hata J, Matsumura K, Iida M, Kiyohara Y (2008) High-sensitivity C-reactive protein and coronary heart disease in a general population of Japanese: the Hisayama study. Arterioscler Thromb Vasc Biol 28:1385–1391
Makita S, Nakamura M, Satoh K, Tanaka F, Onoda T, Kawamura K, Ohsawa M, Tanno K, Itai K, Sakata K, Okayama A, Terayama Y, Yoshida Y, Ogawa A (2009) Serum C-reactive protein levels can be used to predict future ischemic stroke and mortality in Japanese men from the general population. Atherosclerosis 204:234–238
Iso H, Cui R, Date C, Kikuchi S, Tamakoshi A, JACC Study Group (2009) C-reactive protein levels and risk of mortality from cardiovascular disease in Japanese: the JACC study. Atherosclerosis 207:291–297
Albert MA, Glynn RJ, Buring J, Ridker PM (2004) C-reactive protein levels among women of various ethnic groups living in the United States (from the Women's Health Study). Am J Cardiol 93:1238–1242
Khera A, McGuire DK, Murphy SA, Stanek HG, Das SR, Vongpatanasin W, Wians FH Jr, Grundy SM, de Lemos JA (2005) Race and gender differences in C-reactive protein levels. J Am Coll Cardiol 46:464–469
Koh JM, Khang YH, Jung CH, Bae S, Kim DJ, Chung YE, Kim GS (2005) Higher circulating hsCRP levels are associated with lower bone mineral density in healthy pre- and postmenopausal women: evidence for a link between systemic inflammation and osteoporosis. Osteoporos Int 16:1263–1271
Ding C, Parameswaran V, Udayan R, Burgess J, Jones G (2008) Circulating levels of inflammatory markers predict change in bone mineral density and resorption in older adults: a longitudinal study. J Clin Endocrinol Metab 93:1952–1958
Kim BJ, Yu YM, Kim EN, Chung YE, Koh JM, Kim GS (2007) Relationship between serum hsCRP concentration and biochemical bone turnover markers in healthy pre- and postmenopausal women. Clin Endocrinol 67:152–158
Cesari M, Penninx BW, Pahor M, Lauretani F, Corsi AM, Rhys Williams G, Guralnik JM, Ferrucci L (2004) Inflammatory markers and physical performance in older persons: the InCHIANTI study. J Gerontol A Biol Sci Med Sci 59:242–248
Penninx BW, Kritchevsky SB, Newman AB, Nicklas BJ, Simonsick EM, Rubin S, Nevitt M, Visser M, Harris T, Pahor M (2004) Inflammatory markers and incident mobility limitation in the elderly. J Am Geriatr Soc 52:1105–1113
Cesari M, Kritchevsky SB, Baumgartner RN, Atkinson HH, Penninx BW, Lenchik L, Palla SL, Ambrosius WT, Tracy RP, Pahor M (2005) Sarcopenia, obesity, and inflammation-results from the Trial of Angiotensin Converting Enzyme Inhibition and Novel Cardiovascular Risk Factors Study. Am J Clin Nutr 82:428–434
Tankó LB, Christiansen C, Cox DA, Geiger MJ, McNabb MA, Cummings SR (2005) Relationship between osteoporosis and cardiovascular disease in postmenopausal women. J Bone Miner Res 20:1912–1920
Bagger YZ, Rasmussen HB, Alexandersen P, Werge T, Christiansen C, Tankó LB, PERF study group (2007) Links between cardiovascular disease and osteoporosis in postmenopausal women: serum lipids or atherosclerosis per se? Osteoporos Int 18:505–512
Demer LL, Tintut Y (2008) Vascular calcification: pathobiology of a multifaceted disease. Circulation 117:2938–2948
Labarrere CA, Zaloga GP (2004) C-reactive protein: from innocent bystander to pivotal mediator of atherosclerosis. Am J Med 117:499–507
Nakamura K, Tsugawa N, Saito T, Ishikawa M, Tsuchiya Y, Hyodo K, Maruyama K, Oshiki R, Kobayashi R, Nashimoto M, Yoshihara A, Ozaki R, Okano T, Yamamoto M (2008) Vitamin D status, bone mass, and bone metabolism in home-dwelling postmenopausal Japanese women: Yokogoshi Study. Bone 42:271–277
We wish to thank the staff of the Muramatsu Health Center for their help with data collection. We are also grateful to the following institutions for providing us with necessary medical data: Igarashi Orthopaedic Clinic, Ishizone Clinic, Ito Clinic, Kaneko Clinic, Kasahara Clinic, Koyama Orthopaedic Clinic, Nanbugo General Hospital, Nanbugo Kosei Hospital, Murata Clinic, Takeda Clinic, Yamamura Orthopaedic Clinic in Gosen City, Kaetsu Hospital, Kameda-Daiichi Hospital, Nekoyama Miyao Hospital in Niigata City, and Tominaga Kusano Hospital in Sanjo City. This study was supported in part by a Grant-in-Aid for Scientific Research (C) No.40339958 from the Japanese Ministry of Education, Culture, Sports, Science and Technology.
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Nakamura, K., Saito, T., Kobayashi, R. et al. C-reactive protein predicts incident fracture in community-dwelling elderly Japanese women: the Muramatsu study. Osteoporos Int 22, 2145–2150 (2011). https://doi.org/10.1007/s00198-010-1425-9
- Cohort studies
- C-reactive protein