D V Doyle

Incidence and risk factors for radiographic knee osteoarthritis in middle-aged women : The Chingford Study

OBJECTIVE To examine the natural history, role of risk factors, and incidence of knee osteoarthritis (OA) in a prospective study of women from a population cohort. METHODS Women from the Chingford Study who had been recruited in 1989 were followed up with knee radiographs 4 years later. A total of 715 paired radiographs (71% of the original sample) were graded for osteophytes and 644 for joint space narrowing (JSN). Women whose radiographs had been graded as 0 in 1989 and as > or =14 years later were classified as having incident disease. Incident cases were compared with controls for associations with a number of risk factors. RESULTS Eighty-one women (12.6%) developed JSN of the knee, equating to an incidence of 3.1% per year. No clear risk factors for JSN were identified. Reproducibility of measures of joint space is poor, however, leading to inaccuracy of definition. Incident knee osteophytes developed in 95 women (133%), equating to an incidence of 3.3% per year. Compared with controls, women with incident knee osteophytes were older, heavier, and had more hand OA and knee symptoms. Women in the top tertile of obesity (body mass index >26.4) had a significantly increased risk of incident knee osteophytes (odds ratio [OR] 2.38, 95% confidence interval [95% CI] 1.29-4.39). Incident knee osteophytes increased by 20% per 5-year age increase. A nonsignificant protective effect for incident knee osteophytes was seen with current estrogen replacement therapy (ERT) (OR 0.41, 95% CI 0.12-1.42). No effect was associated with smoking, physical activity, hysterectomy, or previous knee injury. CONCLUSION Obesity and aging are associated with a high risk of new knee OA developing in women. Evidence of a protective effect of ERT was seen. No clear association was found for incident JSN, suggesting that different etiologic mechanisms are operating or that standard radiographs are an inaccurate measure of incident narrowing.

The relationship between osteoarthritis and osteoporosis in the general population: the Chingford Study.

OBJECTIVE--A total of 979 women from the Chingford general population survey were studied to examine the hypothesis that osteoarthritis (OA) and osteoporosis are inversely related. METHODS--All women had radiographs of the hands and knees. A total of 579 also had AP radiographs of the lumbar spine which were graded for the presence of osteophytes. All women had bone densitometry performed at the lumbar spine (L1-L4) and femoral neck. Mean bone densities (BMD) were compared between those with disease and those with no disease at any other sites. All results were adjusted for age and body mass index (BMI). RESULTS--All OA groups had significantly higher bone density than controls at the lumbar spine. For distal interphalangeal (DIP) OA (n = 140) the difference was +5.8% (+3.0, +8.6), for carpometacarpal (CMC) OA (n = 160) +3.0% (+0.1, +5.9), for knee OA (n = 118) +7.6% (+4.3, +10.9), and lumbar spine OA (LSOA) (n = 194) +7.8% (+6.0, +8.8). Those with generalised OA (GOA n = 22), a combination of knee, DIP and CMC OA had an increase of +9.3 (+2.0, +16.6). For the femoral neck BMD was also increased significantly ranging from +2.5% for the CMC, +6.2% for the knee and +6.3% in the lumbar spine OA group. The risk of knee OA for women in the top tertile of BMD was 2.13 (1.15-3.93). Additional adjustment for other confounders such as smoking, alcohol, exercise, HRT, social class and spine osteophytes did not alter the results. CONCLUSIONS--These results suggest that small increases in BMD are present in middle aged women with early radiological OA of the hands, knees and lumbar spine. These data support the hypothesis that the two conditions are inversely related, although the mechanisms remain unclear.

Incidence and progression of osteoarthritis in women with unilateral knee disease in the general population: the effect of obesity.

OBJECTIVES--The natural history of knee osteoarthritis (OA) is poorly understood. The principal aim was to assess the rate of contralateral knee OA in middle aged women in the general population with existing unilateral disease and to identify the major factors that influence this rate. METHODS--Fifty eight women aged (45-64) from a general population study cohort were identified with unilateral knee OA diagnosed radiologically (Kellgren and Lawrence 2+) (K&L). Follow up AP films were obtained at 24 months and compared with the baseline for K&L grade and individual features of osteophytes and joint space. RESULTS--Twenty women (34%) developed incident disease in the contralateral knee (based on K&L 2+ or osteophyte changes) and 22.4% (n = 13) of women progressed radiologically in the index joint. Obesity at baseline was the most important factor related to incident disease, 47% of women in the top BMI tertile developed OA, compared with 10% in the lowest tertile: relative risk 4.69 (063-34.75). No clear effect was seen for age, physical activity, trauma or presence of hand OA. CONCLUSIONS--Over one third of middle aged women with unilateral disease will progress to bilateral knee OA within two years and a fifth will progress in the index joint. Obesity is a strong and important risk factor in the primary and secondary prevention of OA. These natural history data provide a useful estimate for planning therapeutic intervention trials.

Definition of osteoarthritis of the knee for epidemiological studies.

OBJECTIVES--There are no agreed criteria for osteoarthritis (OA) of the knee in population studies. The radiographic scoring system of Kellgren and Lawrence has been the system most used in the past and although other methods have been developed, comparisons have not been performed. Therefore these grading systems were compared in radiographs from a general population sample. METHODS--Anteroposterior weightbearing radiographs of 1954 knees from 977 women aged 45-64 years from the Chingford population study were read by a variety of methods, including quantitative measures of minimum joint space, qualitative measures of osteophytes and of joint space, and a qualitative Kellgren and Lawrence global score. All qualitative methods used standardised atlases. Intra-observer and interobserver reproducibility was tested on a subgroup of 100 films using three observers and two readings. Variables were dichotomised at the tenth and second centiles to define OA. Odds ratios were calculated for each method for the association of OA with knee pain, obesity, and with each of the other methods. RESULTS--Most methods had high intraobserver and interobserver reproducibility, except for measurements of lateral joint space. The best predictors of knee pain were the presence of osteophytes and the Kellgren and Lawrence grade. Methods measuring narrowing performed less well, with measurements of lateral joint space being particularly poor. Similar results were achieved in the comparison with obesity and in the comparisons between methods. CONCLUSIONS--These data suggest that the presence or absence of a definite osteophyte read by a single observer with an atlas is the best method of defining OA of the knee for epidemiological studies in women. Assessment of narrowing may be better used in evaluating severity.

Bone mineral density and vertebral compression fracture rates in ankylosing spondylitis.

OBJECTIVE--To examine the relationship between disease severity and bone density as well as vertebral fracture risk in patients with ankylosing spondylitis (AS). METHODS--Measurements were taken for bone mineral density (BMD) and vertebral fracture rates in 87 patients with AS. BMD was measured at the hip (femoral neck -FN), lumbar spine (L1-L4-LS) and for the whole body using a hologic-QDR-1000/W absorptiometer. An algorithm based on normal female ranges of vertebral heights was used to define a fracture as occurring when two vertebral ratios were each three standard deviations below the calculated mean of the controls. RESULTS--Patients with AS had significantly lower FN-BMD in proportion to disease severity (based on a Schober index) and disease duration. LS-BMD was also reduced in early disease, but in patients with advanced AS it had increased considerably. Nine vertebral fractures (10.3%) were identified which was considerably higher than expected when compared with a fracture of 1.9% in a control population of 1035 females of a similar age range. Patients with AS with fractures were significantly older, more likely to be male, had longer disease duration and more advanced spinal limitation with less mobility. There was no significant reduction in lumbar spine or femoral neck bone density in the fracture group. CONCLUSIONS--Vertebral fractures that result from osteoporosis are a feature of longstanding AS. BMD used as a measure of osteoporosis of the spine in advanced AS is unreliable probably as a result of syndesmophyte formation and does not predict the risk of vertebral fracture. Alternative sites such as the neck of the femur should be used for sequential assessment of BMD in AS.

Is hormone replacement therapy protective for hand and knee osteoarthritis in women?: The Chingford study

OBJECTIVES To explore whether hormone replacement therapy (HRT) has a protective role for osteoarthritis (OA) of the hand and knee in a cross sectional study of women in the general population. METHODS 1003 women aged 45-64 (mean age 54.2) from the Chingford Study were asked details of HRT use. Standard anteroposterior radiographs of hands, knees were taken and scored according to the methods of Kellgren and Lawrence (grade 2+ positive for OA), and using individual features of osteophytes and joint space narrowing. Analysis compared ever use (> 12 months) versus never use, and current use (> 12 months) versus never use. Only 606 definitely postmenopausal women were included in the analysis. Odds ratios and 95% confidence intervals were calculated using logistic regression for risk of user versus non-user at each site, adjusted for age, height and weight, menopausal age and for bone mineral density of the femoral neck. RESULTS For current users (n=72) there was a significant protective effect of HRT for knee OA (defined by Kellgren and Lawrence grade or osteophytes 0.31 (95% CI 0.11, 0.93), and a similar but not significant effect for moderate joint space narrowing of the knee, 0.41 (95% CI 0.05, 3.15) and for distal interphalangeal OA 0.48 (95% CI 0.17, 1.42). No clear effect was seen for the carpometacarpal joint, CMC OA 0.94 (95% CI 0.44, 2.03). When analysing ever users (n=129) the protective effect was reduced. For ex-users of >12 months (mean duration 40.7 months), there was no overall protective effect of HRT for OA. Additional adjustment for hysterectomy, physical activity, social class, and smoking made little difference to the results. CONCLUSIONS These data show an inverse association of current HRT use and radiological OA of the knee suggestive of a protective effect. The effect was weaker in the hand joints. The mechanism of the protection is unclear but has important implications for aetiopathogenesis.

The relationship of bone density and fracture to incident and progressive radiographic osteoarthritis of the knee: The Chingford study

OBJECTIVE Investigators performing cross-sectional studies have reported small increases in bone mineral density (BMD) in subjects with osteoarthritis (OA). This study was undertaken to examine the association of bone mass with incident and progressive disease and to determine whether prior fractures influence the development of OA. METHODS Eight hundred thirty women had repeat knee radiographs 48 months from baseline. All radiographs were graded on the presence or absence of osteophytes and joint space narrowing (JSN). Incident knee OA was defined as new disease in the 715 women without knee OA at baseline. Progression was a change of at least one grade in the 115 women with baseline knee OA. All women underwent bone densitometry of the lumbar spine and hip. Rates of subsequent incident OA were compared between fracture groups. RESULTS The 95 women with incident knee osteophytes had significantly higher baseline spine BMD (1.01 gm/cm2 versus 0.95 gm/cm2, or 6.3%; P = 0.002) and significantly higher hip BMD (0.79 gm/cm2 versus 0.76 gm/cm2, or 3.9%; P = 0.02) than those without incident disease. For the 33 women whose osteophytes progressed, no difference was seen compared with nonprogressors in spine BMD, but hip BMD was modestly reduced (-2.5%). The 81 women who had incident JSN had nonsignificantly higher baseline spine BMD (3.0%), while no difference was seen for the 30 women whose JSN had progressed. For hip BMD, a nonsignificant increase was seen in those with incident JSN (1.3%), and a nonsignificant reduction was seen in those whose JSN progressed (-2.7%). One hundred forty-five women sustained peripheral fractures, mainly in the distal forearm (27.6%) and vertebrae (28.3%). Women with a peripheral fracture had a reduced risk of subsequently developing incident knee OA (odds ratio [OR] 0.30, 95% confidence interval [95% CI] 0.11-0.84). Although numbers were smaller, nonsignificant reductions in rates of incident OA were seen for those with distal forearm (OR 0.40, 95% CI 0.11-1.49) and vertebral (OR 0.20, 95% CI 0.07-1.61) fractures. CONCLUSION These results confirm that for women who develop incident knee OA, defined by osteophytes, BMD is higher and of a magnitude similar to that shown in cross-sectional studies. Low BMD at the hip appears weakly related to progression. Women with previous fractures have less chance of developing OA, independent of BMD status. Although the mechanism for this action is unclear, these results suggest a possible common role of bone turnover and repair in the early manifestations of OA.

An articular index for the assessment of osteoarthritis.

An articular index was devised for the sequential assessment of patients with osteoarthritis (OA). Forty-eight joint units, chosen to reflect the characteristic pattern of the disease, were scored for tenderness on pressure or movement on a 4-point scale. Four observers examined patients to assess inter- and intraobserver error. The index was highly reproducible both within and between observers; intraobserver error was, however, significantly smaller. In a double-blind, cross-over trial the index was sufficiently sensitive to detect a statistically significant difference between the responses of patients with OA to an anti-inflammatory agent and to a simple analgesic. It is likely to be a useful addition to current methods of measurement in osteoarthritis.

Relation between insulin-like growth factor-I concentrations, osteoarthritis, bone density, and fractures in the general population: the Chingford study.

OBJECTIVE: To assess the association between serum insulin-like growth factor-I (IGF-1) concentrations and osteoarthritis, and bone mineral density, and fractures in a large group of middle aged women from the general population. METHODS: 761 women aged 44-64 years from the Chingford study had serum IGF-I concentrations measured; hand, hip, spine, and anteroposterior weight bearing knee radiographs taken; and dual energy x ray absorptiometry (DEXA) scans of the hip and spine. X rays were scored using the Kellgren and Lawrence system. In addition knee x rays were scored using a standard atlas for individual features of osteophytes and joint space narrowing (both graded 0-3). IGF-I concentrations were adjusted for the effects of age. RESULTS: In the osteoarthritis analysis results were compared to a constant group of 155 subjects with no evidence of osteoarthritis at any site. There was no significant difference in serum IGF-I between these subjects and 606 subjects with osteoarthritis at any site. When individual sites were analysed, serum IGF-I was higher in those cases with more severe bilateral knee osteoarthritis and in those with distal interphalangeal (DIP) joint disease. There was no significant association between serum IGF-I and other forms of osteoarthritis or milder forms of knee osteoarthritis. There was no correlation between IGF-I concentrations and bone mineral density at the spine or hip, nor any difference between IGF-I concentrations in subjects with and without a history of non-traumatic fracture [22.8 (SD 6.6) v 23.1 (SD 6.6) nmol litre-1, P = 0.6] CONCLUSIONS: There is a modest association between IGF-I concentrations and the development of DIP osteoarthritis and more severe or bilateral knee joint osteoarthritis in women from the normal population, but no association with other forms of osteoarthritis, bone density, or fractures.

Effects of cyclical etidronate combined with calcitriol versus cyclical etidronate alone on spine and femoral neck bone mineral density in postmenopausal osteoporotic women

OBJECTIVES Few data are available on the effects of combination therapy for the treatment of osteoporosis. The aim of this study was to compare the effects of intermittent cyclical etidronate (E) therapy alone with a combination of cyclical etidronate and calcitriol (E+C) on spine and femoral neck bone mineral density (BMD) at one year. METHODS Postmenopausal women with at least one non-traumatic vertebral fracture or z score < −1.5 were randomly allocated to an E group (each cycle = oral etidronate 400 mg daily for 14 days followed by calcium 500 mg daily for 76 days) or an E+C group (as for E plus oral calcitriol 0.5 μg daily). Lumbar spine and femoral neck BMDs were measured by dual energy x ray absorptiometry at baseline and at one year. The study design did not contain a placebo group. RESULTS The mean % increase in lumbar spine BMD was 5.2% (95%CI= 3.4 to 7.0) in the E+C group (n=24), which was significantly greater than the 2.7% (95%CI= 1.3 to 4.1) increase in the E group (n=23) (p<0.05). The femoral neck BMD in the E+C group increased by 2.0% (95%CI= 0.8 to 3.2), which was significantly different from the E group where there was a −0.4% (95%CI=−2.4 to 1.6) change (p=0.046). CONCLUSIONS These data show that a combination of cyclical etidronate and calcitriol is better than cyclical etidronate alone in terms of changes in BMD at both spine and femoral neck sites. Although further data are needed on fracture efficacy, this study suggests that combination therapies have additive therapeutic potential that may exceed that expected from their theoretical mode of action.