Lower Prevalence of Chondrocalcinosis in Chinese Subjects in Beijing Than in White Subjects in the United States

Transcription

1 ARTHRITIS & RHEUMATISM Vol. 54, No. 11, November 2006, pp DOI /art , American College of Rheumatology Lower Prevalence of Chondrocalcinosis in Chinese Subjects in Beijing Than in White Subjects in the United States The Beijing Osteoarthritis Study Yuqing Zhang, 1 Robert Terkeltaub, 2 Michael Nevitt, 3 Ling Xu, 4 Tuhina Neogi, 1 Piaran Aliabadi, 5 Jingbo Niu, 1 and David T. Felson 1 Objective. Chondrocalcinosis, which can promote joint inflammation and cartilage degeneration, is highly prevalent in elderly white subjects. Data on its prevalence are scarce in other ethnic populations. This study was undertaken to compare the prevalence of chondrocalcinosis in Chinese subjects with that in white subjects. Methods. We recruited a random sample of Beijing residents ages >60 years. Participants underwent standard weight-bearing anteroposterior knee radiography and posteroanterior hand radiography using the protocols developed in the Framingham Osteoarthritis Study. Radiographic chondrocalcinosis was defined as present in a knee or wrist when there was evidence of definite linear cartilage calcification. We compared the prevalence of chondrocalcinosis in Chinese subjects with that in white subjects using age-standardized prevalence ratios. We used identical methods to collect samples of tap water from 2 cities and measured their Supported by the NIH (grants AR-43873, AR-47785, and P01-AG-07996) and the Department of Veterans Affairs Research Service. 1 Yuqing Zhang, DSc, Tuhina Neogi, MD, FRCPC, Jingbo Niu, MD, David T. Felson, MD, MPH: Boston University Medical Center, and Boston University School of Medicine, Boston, Massachusetts; 2 Robert Terkeltaub, MD: VA Medical Center, and University of California, San Diego; 3 Michael Nevitt, PhD: University of California, San Francisco; 4 Ling Xu, MD: Peking Union Medical College Hospital, Beijing, China; 5 Piaran Aliabadi, MD: Brigham and Women s Hospital, Boston, Massachusetts. Dr. Terkeltaub receives support from Eli Lilly for chondrocalcinosis studies. Address correspondence and reprint requests to Yuqing Zhang, DSc, Boston University School of Medicine, Room A203, 715 Albany Street, Boston, MA yuqing@bu.edu. Submitted for publication March 28, 2006; accepted in revised form July 26, levels of calcium, magnesium, and phosphate in the same laboratory. Results. Chinese subjects had a much lower prevalence of knee chondrocalcinosis (1.8% in men, 2.7% in women) than did white subjects (6.2% in men, 7.7% in women), with the age-standardized prevalence ratio being 0.34 (95% confidence interval [95% CI] ) and 0.43 (95% CI ) in men and women, respectively. Wrist chondrocalcinosis was rare in elderly Chinese subjects (prevalence 0.3% in men and 1.0% in women), with the age-standardized prevalence ratio being 0.06 (95% CI ) in Chinese men and 0.18 (95% CI ) in Chinese women. Calcium levels in the tap water in Beijing were 15-fold higher than in Framingham, whereas no difference was found in magnesium and phosphate levels. Conclusion. Knee chondrocalcinosis and wrist chondrocalcinosis are far less common in Chinese subjects in Beijing than in US white subjects in Framingham, Massachusetts. Given the current lack of understanding of the etiology of chondrocalcinosis, further epidemiologic studies of the impact of genetic and environmental factors on occurrence of chondrocalcinosis are indicated. Calcium pyrophosphate dihydrate (CPPD) crystal deposition in articular fibrocartilage and hyaline cartilage, termed chondrocalcinosis, is a common radiographic and pathologic finding associated with both aging and osteoarthritis (OA) (1). Most subjects with chondrocalcinosis are asymptomatic, but CPPD crystal deposition can promote articular cartilage degeneration (pseudo-oa), and traffic of the crystals from articular cartilage into the joint space can stimulate acute syno- 3508

2 PREVALENCE OF CHONDROCALCINOSIS IN CHINESE VS. WHITE SUBJECTS 3509 vitis (pseudogout) as well as chronic proliferative pseudorheumatoid synovitis (2). Most epidemiologic studies of chondrocalcinosis have been conducted with white subjects (3); we are unaware of any studies that have compared differences in the prevalence of chondrocalcinosis among ethnic groups. Epidemiologic studies of disease in different racial or ethnic groups frequently reveal major differences in disease occurrence and often provide important clues about possible determinants of a disease. Knee chondrocalcinosis is positively associated with the prevalence of knee OA (4,5). Previously, we reported that the prevalence of knee OA in Chinese men in Beijing is similar to that in white men in the US, and that the prevalence of knee OA in Chinese women in Beijing is higher than that in white women in the US (6). These findings prompted us to speculate that elderly Chinese subjects in Beijing might have a higher prevalence of radiographic knee chondrocalcinosis than do white subjects in the US. Thus, we conducted a population-based survey among elderly Chinese subjects in Beijing, using the same instruments and protocols that were previously used to define and ascertain chondrocalcinosis in the Framingham OA Study (7). We estimated the prevalence of radiographic chondrocalcinosis of the knee and wrist in the elderly Chinese population in Beijing and compared it with the prevalence in the elderly white population in the US. SUBJECTS AND METHODS Recruitment of subjects. The Beijing OA Study. We recruited a random sample of men and women ages 60 years from 4 central districts of Beijing, China. Subjects were interviewed at their homes by trained health professionals. At the end of the interview, subjects were invited to the central examination site at Peking Union Medical College Hospital for radiography. To acquire hand and knee radiographs, we adapted the same protocols used in the Framingham OA Study, and used the equivalent radiographic films as well as the same exposure time (5 8.3 ma) and imaging voltage (70 kvp). A bone and joint radiologist who participated in the Framingham OA Study compared initial images from the Beijing OA Study with images from the Framingham OA Study and directed appropriate changes in radiography parameters so that image exposure and contrast were equivalent in both studies. All subjects received weight-bearing anteroposterior (AP) radiographs of both knees and posteroanterior (PA) radiographs of both hands. Transportation to the hospital was provided (6). The Framingham OA Study. The comparison group consisted of 2 cohorts of the Framingham OA Study, the Framingham Original Cohort and the Framingham Offspring Cohort. Between 1992 and 1993, 1,412 subjects in the Framingham Original Cohort (ages years) received weightbearing AP radiographs of both knees and PA radiographs of both hands (8). Between 1993 and 1994, 1,523 subjects (ages years) in the Framingham Offspring Cohort received weight-bearing AP knee radiographs and PA hand radiographs. Four hundred forty-two of the latter subjects were 60 years old. Radiography protocols in the Framingham Offspring Cohort were the same as those in the Framingham Original Cohort. All subjects in the Framingham OA Study were white. Reading of radiographs. A single bone and joint radiologist (PA) read all knee and hand radiographs obtained in the Beijing OA Study according to the reading protocols of the Framingham OA Study. Radiographic chondrocalcinosis was considered to be present in the knee or wrist when evidence of definite linear cartilage calcification was present. To check the reliability of radiograph reading, a rheumatologist reread the knee and hand radiographs of subjects ages 80 years. The kappa statistic for interreader reliability in determining presence or absence of chondrocalcinosis was 0.79 (95% confidence interval [95% CI] ) for the knee and 0.65 (95% CI ) for the wrist. Assessment of levels of calcium, magnesium, and phosphate in tap water. We collected 2 samples of tap water from 1 resident at each of 4 districts in Beijing (total of 8 samples) and 4 samples from 1 resident in Framingham, Massachusetts, using bottles provided by Massachusetts Geo- Labs (Braintree, MA). All water samples from Beijing and 2 samples from Framingham were tested in the laboratory at the Beijing Environmental Protection Agency. The remaining 2 samples from Framingham were tested at Massachusetts Geo- Labs. Both laboratories used the same methods to assess the levels of calcium (9), magnesium (9), and total phosphate (10) in the water samples. Statistical analysis. We divided the subjects into 5 age groups, as follows: years, years, years, years, and 80 years. We calculated the age-specific prevalence of radiographic knee and wrist chondrocalcinosis for Chinese men and women separately. Subjects who selfreported rheumatoid arthritis (RA), subjects whose hand or knee radiographs revealed typical radiographic evidence of RA, and subjects who reported taking medications commonly used to treat RA (e.g., methotrexate, gold, or antimalarial medication) were excluded from the Framingham OA Study and the Beijing OA Study. To compare the prevalence of radiographic knee chondrocalcinosis in Chinese subjects in Beijing with that found in white subjects in Framingham, we excluded Framingham subjects 60 years old because all participants in the Beijing OA Figure 1. Prevalence of radiographic knee chondrocalcinosis in Chinese and white subjects, by sex and age group.

3 3510 ZHANG ET AL Figure 2. Prevalence of radiographic wrist chondrocalcinosis in Chinese and white subjects, by sex and age group. Study were 60 years old. We applied the age-specific prevalence of knee chondrocalcinosis in the Framingham OA Study to the age distribution of the Beijing OA Study, and calculated an age-standardized prevalence ratio and its 95% CI. We used the same approach to compare the prevalence of radiographic wrist chondrocalcinosis between the 2 groups. RESULTS Of the 3,277 age-eligible subjects we contacted during door-to-door canvassing in Beijing from January 1998 to June 2001, 2,506 (76.5%) had a clinical examination and knee radiographs. Of those, 3 subjects who had RA and 3 subjects whose knee radiographs could not be assessed were excluded from the analysis. Only 1 subject, who was also excluded, had had a unilateral total knee replacement. Details on those who completed versus those who did not complete the home interview and examination have been reported elsewhere (6,11). In general, elderly Chinese subjects in Beijing were thinner than elderly subjects in Framingham (mean body mass index 25.3 kg/m 2 in men and 26.0 kg/m 2 in women), and many Chinese subjects had low levels of educational attainment. Figure 1 depicts the sex- and age-specific prevalence of knee chondrocalcinosis in Chinese subjects in Beijing and white subjects in Framingham. The prevalence of radiographic knee chondrocalcinosis increased with age in all groups and was more common in women than in men. In each age group, the prevalence of chondrocalcinosis in both men and women was much lower in Chinese subjects than in white subjects. Radiographic wrist chondrocalcinosis was very rare among elderly Chinese subjects. Of the 2,510 participants who had hand radiographs, only 3 Chinese men and 15 Chinese women had radiographic wrist chondrocalcinosis. The prevalence of wrist chondrocalcinosis in each age group in Chinese subjects was much lower than that in white subjects for both men and women (Figure 2). The age-standardized prevalence of knee chondrocalcinosis in Chinese men was only one-third of that observed in white men (Table 1), and the difference was significant for bilateral disease (age-standardized prevalence ratio 0.20, 95% CI , P 0.001) but not for unilateral disease (age-standardized prevalence ratio 1.21, 95% CI , P 0.64) (data not shown). A similar difference was observed in women. Compared with white subjects, Chinese men and women had a much lower prevalence of radiographic chondrocalcinosis in the wrist, with age-standardized prevalence ratios of 0.06 (P 0.001) and 0.18 (P 0.001), respectively. On average, calcium levels in tap water from Beijing (67.6 mg/liter) were 15-fold higher than those in Framingham (4.5 mg/liter). No difference was found in the levels of magnesium. Phosphate was undetectable in water samples from either city. DISCUSSION Despite a high prevalence of radiographic knee OA in Beijing, China, the prevalence of radiographic knee and wrist chondrocalcinosis is much lower in Table 1. Comparison of the prevalence of knee and wrist chondrocalcinosis among Chinese subjects in Beijing and white subjects in Framingham, MA Crude prevalence, % Age-standardized prevalence ratio Chinese subjects White subjects (95% CI)* Men Knee chondrocalcinosis ( ) Wrist chondrocalcinosis ( ) Women Knee chondrocalcinosis ( ) Wrist chondrocalcinosis ( ) * 95% CI 95% confidence interval. P

4 PREVALENCE OF CHONDROCALCINOSIS IN CHINESE VS. WHITE SUBJECTS 3511 elderly Chinese subjects in Beijing than in white subjects in Framingham, Massachusetts. This is especially the case for bilateral chondrocalcinosis. While unilateral chondrocalcinosis often occurs secondary to joint injury (12), the bilateral condition is more likely to be the result of a systemic predilection. Our findings suggest that Chinese subjects in Beijing may lack a systemic predisposition to chondrocalcinosis. Several metabolic and endocrine disorders, i.e., hyperparathyroidism, hemochromatosis, hypomagnesemia, and hypophosphatasia, have been found to be associated with the occurrence of chondrocalcinosis (3,13 15). These disorders appear to induce chondrocalcinosis through intraarticular dysregulation of inorganic pyrophosphate metabolism. Studies have shown that free serum calcium concentration is the major determinant of the rate of parathyroid hormone (PTH) secretion (16), and even slight reductions in serum calcium levels will increase the rate of PTH secretion by normal parathyroid glands (17). Primary hyperparathyroidism, a disease caused by glandular hyperplasia that typically presents after age 50, appears to be rare in Beijing in comparison with New York City (18). In the current study, we collected samples of tap water from residents in Beijing and Framingham and tested the levels of calcium, magnesium, and total phosphate in the same laboratory using standard methods. Levels of calcium in the tap water in Beijing were fold higher than those in Framingham, but no such difference was observed in the levels of magnesium and phosphate. We speculate that the high levels of calcium found in the drinking water in Beijing may affect PTH secretion and, as a consequence, lead to a lower prevalence of chondrocalcinosis among elderly subjects in Beijing. Valid methods for comparing the prevalence of chondrocalcinosis in Chinese subjects with that in white subjects were incorporated into the design of this study. Participants were recruited from the general population, and the same methods were used to assess chondrocalcinosis in both groups. Thus, the difference in the prevalence of chondrocalcinosis found between the 2 racial groups is unlikely to be a result of sampling or assessment bias. Furthermore, as in other studies (3), we found that radiographic knee chondrocalcinosis and wrist chondrocalcinosis were more common in women than in men, and that the prevalence increased with age. All of this evidence suggests that differences in the prevalence of chondrocalcinosis do exist between Chinese subjects and white subjects. Our study has some limitations. First, the data on the prevalence of radiographic knee and wrist chondrocalcinosis in Chinese subjects and in white subjects were derived from the populations of 2 isolated areas; thus, one may question whether the difference in the prevalence of chondrocalcinosis can be generalized to the larger racial or geographic areas from which the study samples were selected. Second, linear deposits of calcification in human meniscal fibrocartilage and hyaline articular cartilage detectable by plain radiography are recognized to comprise principally CPPD (19). Moreover, CPPD is the major form of chondrocalcinosis in the meniscal fibrocartilage even though both basic calcium phosphate (BCP) (e.g., hydroxyapatite) and CPPD crystals are often concurrently deposited in joint cartilage (20). However, although it can be used to detect BCP crystal deposition in periarticular soft tissue, plain radiography is not sensitive enough to detect the vast majority of BCP deposits in joint cartilage (21); thus, it is plausible that there may be distinctions in BCP crystal deposition in the joint cartilage between populations that we were unable to address using plain radiography in this study. Third, it is likely that some of the articular CPPD deposition searched for in this study was microscopic and not visible on radiography. As a result, the prevalence of chondrocalcinosis may have been underestimated in both populations. Fourth, while calcium levels in the tap water were higher in Beijing than in Framingham, we did not compare the total dietary calcium intake of the 2 populations. It is likely that dairy product consumption was substantially higher in Framingham than in Beijing. Other factors that may affect serum calcium levels, such as thiazides and calcium-containing antacids, were not evaluated in this study. Finally, we did not measure levels of serum calcium, PTH, vitamin D, or other elements in the drinking water that may potentially impact the occurrence of chondrocalcinosis. This is the first study to demonstrate a major difference in the prevalence of chondrocalcinosis among different racial groups by direct comparison using a standardized assessment method. We speculate that the low prevalence of chondrocalcinosis in Beijing might be related to the hard water in Beijing, but this relationship needs further study. Effective, rational therapies to prevent or lessen idiopathic CPPD crystal deposition are currently lacking. Further exploration of these potential ethnic differences in chondrocalcinosis might provide clues to etiology and, in turn, to treatment.

5 3512 ZHANG ET AL REFERENCES 1. Wu CW, Terkeltaub R, Kalunian KC. Calcium-containing crystals and osteoarthritis: implications for the clinician. Curr Rheumatol Rep 2005;7: Swan A, Heywood B, Chapman B, Seward H, Dieppe P. Evidence for a causal relationship between the structure, size, and load of calcium pyrophosphate dihydrate crystals, and attacks of pseudogout. Ann Rheum Dis 1995;54: Silman AJ. Calcium pyrophosphate dihydrate (CPPD) deposition disease. In: Hochberg M, editor. Epidemiology of the rheumatic disease. 2nd ed. Oxford: Oxford University Press; p Sanmarti R, Kanterewicz E, Pladevall M, Panella D, Tarradellas JB, Gomez JM. Analysis of the association between chondrocalcinosis and osteoarthritis: a community based study. Ann Rheum Dis 1996;55: Felson DT, Anderson JJ, Naimark A, Kannel W, Meenan RF. The prevalence of chondrocalcinosis in the elderly and its association with knee osteoarthritis: the Framingham Study. J Rheumatol 1989;16: Zhang Y, Xu L, Nevitt MC, Aliabadi P, Yu W, Qin M, et al. Comparison of the prevalence of knee osteoarthritis between the elderly Chinese population in Beijing and whites in the United States: the Beijing Osteoarthritis Study. Arthritis Rheum 2001;44: Felson DT, Naimark A, Anderson J, Kazis L, Castelli W, Meenan RD. The prevalence of knee osteoarthritis in the elderly: the Framingham Osteoarthritis Study. Arthritis Rheum 1987;30: Zhang Y, Niu J, Kelly-Hayes M, Chaisson CE, Aliabadi P, Felson DT. Prevalence of symptomatic hand osteoarthritis and its impact on functional status among the elderly: the Framingham Study. Am J Epidemiol 2002;156: Environmental Protection Agency (US). Methods for the determination of metal in environmental samples. Supplement 1-EPA/ 600/R ; May Environmental Protection Agency (US). Methods for chemical analysis of water and wastes. EPA-600/ , Cincinnati: EPA, EMSL; Zhang Y, Xu L, Nevitt MC, Niu J, Goggins JP, Aliabadi P, et al. Lower prevalence of hand osteoarthritis among Chinese subjects in Beijing compared with white subjects in the United States: the Beijing Osteoarthritis Study. Arthritis Rheum 2003;48: Doherty M, Watt I, Dieppe PA. Localised chondrocalcinosis in post-meniscectomy knees. Lancet 1982;1: Glass JS, Grahame R. Chondrocalcinosis after parathyroidectomy. Ann Rheum Dis 1976;35: Rynes RI, Merzig EG. Calcium pyrophosphate crystal deposition disease and hyperparathyroidism: a controlled, prospective study. J Rheumatol 1978;5: Wright GD, Doherty M. Calcium pyrophosphate crystal deposition is not always wear and tear or aging. Ann Rheum Dis 1997;56: Tfelt-Hansen J, Brown EM. The calcium-sensing receptor in normal physiology and pathophysiology: a review. Crit Rev Clin Lab Sci 2005;42: Mihai R, Farndon JR. Parathyroid disease and calcium metabolism. Br J Anaesth 2000;85: Bilezikian JP, Meng X, Shi Y, Silverberg SJ. Primary hyperparathyroidism in women: a tale of two cities New York and Beijing. Int J Fertil Womens Med 2000;45: Genant HK. Roentgenographic aspects of calcium pyrophosphate dihydrate crystal deposition disease (pseudogout). Arthritis Rheum 1976;19: Rosenthal AK, Ryan LM. Calcium pyrophoshate crystal deposition disease, pseudogout, and articular chondrocalcinosis. In: Moreland LW, editor. Arthritis and allied conditions. 15th ed. Philadelphia: Lippincott, Williams & Wilkins; p Halverson PB. Basic calcium phosphate (apatite, octacalcium phosphate, tricalcium phosphate) crystal deposition disease and calcinosis. In: Moreland LW, editor. Arthritis and allied conditions. 15th ed. Philadelphia: Lippincott, Williams & Wilkins; p