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Extended report
The impact of knee and hip chondrocalcinosis on disability in older people: the ProVA Study from northeastern Italy
  1. Estella Musacchio1,
  2. Roberta Ramonda2,
  3. Egle Perissinotto3,
  4. Leonardo Sartori1,
  5. Rosemarie Hirsch4,
  6. Leonardo Punzi2,
  7. Sabina Zambon1,
  8. Maria Chiara Corti5,
  9. Giovannella Baggio6,
  10. Enzo Manzato7,8,
  11. Andrea Doria2,
  12. Gaetano Crepaldi8
  1. 1Clinica Medica I, Department of Medical and Surgical Sciences, University of Padova, Padova, Italy
  2. 2Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Padova, Padova, Italy
  3. 3Department of Environmental Medicine and Public Health, University of Padova, Padova, Italy
  4. 4Center for Disease Control and Prevention, National Center for Health Statistics, Hyattsville, Maryland, USA
  5. 5Azienda ULSS N 16, Padova, Italy
  6. 6Clinica Geriatrica, Department of Medical and Surgical Sciences, University of Padova, Padova, Italy
  7. 7Medicina Generale, Azienda Ospedaliera, University of Padova, Padova, Italy
  8. 8Istituto di Neuroscienze, Aging Branch-National Council for Research, CNR, Padova, Italy
  1. Correspondence to Dr Roberta Ramonda, Rheumatology Unit, Department of Clinical and Experimental Medicine, Azienda Ospedaliera, University of Padova, Via Giustiniani 2, 35128 Padova, Italy; roberta.ramonda{at}


Objectives Chondrocalcinosis is frequently associated with osteoarthritis. The role of osteoarthritis in the onset and progression of disability is well known. The impact of chondrocalcinosis on disability has never been investigated in epidemiological studies.

Methods Progetto Veneto Anziani is a survey of 3099 older Italians, focusing on chronic diseases and disability. Assessment was by questionnaires, physical performance tests and clinical evaluations. Chondrocalcinosis was determined by x-ray readings of 1629 consecutive subjects. Knee and hip osteoarthritis severity was evaluated by summing the radiographic features score (RFS) assigned during x-ray reading.

Results Subjects with chondrocalcinosis were older and more frequently women (age-adjusted p<0.0001). The gender association disappeared following adjustment for osteoarthritis severity. However, at the knee, the prevalence of osteoarthritis was higher in chondrocalcinosis patients independently of age and sex (age-adjusted p<0.0001). No difference was found between chondrocalcinosis and controls in sociodemographic variables and comorbidity. Knee chondrocalcinosis was strongly associated with clinical features of knee osteoarthritis and with disability assessment parameters in the bivariate analysis. Most associations remained after adjusting for age. After further adjustment for RFS, a significant association remained for knee deformity and pain, the need for a cane, difficulty walking 500 m, using a toilet, shopping and repeatedly rising from a chair.

Conclusions Pain and physical function are the outcome measures of choice for assessing disability in osteoarthritis patients. The presence of chondrocalcinosis contributes to both, independently of age and osteoarthritis severity, thus compromising the quality of life and worsening comorbidity.

Statistics from

Chondrocalcinosis is characterised by calcification of articular tissues such as fibro and hyalinecartilage, mainly due to intra-articular calcium pyrophosphate deposition (CPPD). Calcium pyrophosphate-associated arthritis is the third most common inflammatory arthritis. Recognised risk factors are ageing, osteoarthritis, previous joint trauma or injury, metabolic disease and familial predisposition. CPPD may present in variable phenotypes and its complexity is compounded by the use of different terminologies and classifications.1 Chondrocalcinosis can be identified in x-rays or by histological examination. Calcification is not always caused by CPPD and may occur as an isolated finding or coexist with structural changes resembling osteoarthritis.1,,3

Typically affecting individuals over 60 years of age, chondrocalcinosis is reported to be more frequent in women. The relationship between chondrocalcinosis and osteoarthritis, including any underlying mechanisms, is not completely clear. It has been suggested that CPPD may be affected by pyrophosphate levels in the synovial fluid and by cartilage composition.4

We recently reported the prevalence of chondrocalcinosis to be 10.4% in older Italians.5 Chondrocalcinosis was more prevalent in women and increased with age, similar to most epidemiological findings,6,,11 while a recent Chinese study showed a much lower prevalence (2.7%).12

Disability is a common finding in older people and its prevalence is higher in women and increases with age. It can be evaluated by clinical assessment, specific questionnaires and tests measuring the ability to perform activities ranging from basic homecare to physical tasks. It has been demonstrated that these measures provide prognostic information about adverse outcomes.13 14 While osteoarthritis certainly plays an important role in the onset and progression of disability, to our knowledge, no study has investigated the relationship between chondrocalcinosis and disability.

In light of these considerations and of the association between chondrocalcinosis and osteoarthritis, we undertook a study to assess the independent impact of knee and hip chondrocalcinosis on disability in older Italians.

Patients and methods

The population considered was that of the Progetto Veneto Anziani (ProVA) Study, a large observational community-based cohort survey of older people in northeastern Italy. It was designed to provide clinical information on major chronic diseases, measure consequent impairment, evaluate functional limitations and assess disability status.15 The cross-sectional phase ended in 1998, while the longitudinal phase is ongoing. The sampling frame included Caucasians aged 65 years and older, no exclusion criteria were used. The sampling strategy consisted of an age (65–74, 75–84, ≥85 years) and sex-stratified random sample designed to keep the male-to-female ratio at 2:3 and to oversample the oldest old. Oversampling was carried out to provide stable estimates of conditions with low prevalence.

All participants underwent a detailed home interview concerning sociodemographic characteristics, cognitive status, depression, diet, medical history and symptoms, and disability in daily living activities. The participants were then referred to the local hospital for a comprehensive medical and instrumental assessment including x-rays. A board certified physician (geriatrician) reviewed the medical charts and performed a physical examination focusing on rheumatological signs and a battery of specific physical performance tests. A blood sample was obtained from 99% of the participants. Special transportation was provided for the disabled. Home visits by nurses and physicians were arranged for homebound and severely disabled people, with x-rays taken in mobile units.

The study was approved by the local research ethics committee and informed consent was obtained from all participants.


The prevalence of radiographic chondrocalcinosis was investigated in a subpopulation of the ProVA Study cohort, consisting of 1629 consecutive subjects (mean age 75.3±7.3 years; men 75.8±7.6 years, 42%; women 74.9±7.0 years, 58%). Body mass index was calculated as weight (kg) divided by the square of height (m).

x-Ray reading

All x-rays were performed using standardised procedures, with a focus-to-film distance of 100 cm, 55 kV, 8 mA/s. Anteroposterior projection of the hip and extended knee were performed in the orthostatic position, no patellofemoral views were obtained. For the disabled, an alternative position (seated or laying) was recorded. In the case of knee and hip replacements, contralateral joints were read. x-ray reading was performed by expert readers, and hip and knee osteoarthritis was scored according to Altman et al.16 The presence of calcification (chondrocalcinosis) and osteoarthritis features were assessed in the same reading session by two independent readers who periodically underwent quality control procedures.

Knee analysis

The position of subjects was considered, as was the presence of prostheses. Scoring was performed for tibial and femoral osteophytes (grade 0–3), subchondral sclerosis and changes in articular cartilage thickness, measured radiographically as joint space narrowing (JSN) (0–3) and malalignment (0–1). Chondrocalcinosis was recorded as ‘present’ or ‘absent’ in the medial and lateral joint spaces.

Hip analysis

The position of subjects was considered, as was the presence of prostheses. Evaluation included superior and axial coxofemoral JSN (grade 0–3), acetabular and femoral osteophytes (0–3), sclerosis (0–1), erosions (0–1) and deformities of the femoral head (0–1). Chondrocalcinosis was recorded as ‘present’ or ‘absent’ in the pubic symphysis, sacroiliac and coxofemoral space.

Knee and hip osteoarthritis

In accordance with the American College of Rheumatology (ACR) criteria, in the x-ray-read population, knee osteoarthritis was classified on the basis of pain and osteophytes, while hip osteoarthritis was based on pain, osteophytes and JSN.17

Clinical features

Hip and knee osteoarthritis were also assessed in all the 3099 ProVA subjects. Evaluations were carried out blind to the x-ray reading results, and were based on medical history and records, previous x-ray reports, the use of specific analgesics, clinical evaluation including for the knee: deformity, pain at passive movement, reduced passive mobility and crepitus; for the hip: pain at passive movement, rotation and palpation, and reduced external rotation.

Patients with evidence of clinical knee (n=700) and hip (n=463) osteoarthritis were included in the analysis of the association of chondrocalcinosis with osteoarthritis clinical features.

Radiographic features

The number and severity of hip and knee osteoarthritis features were evaluated by summing the scores assigned during x-ray reading. The resulting variable, the radiographic features score (RFS), was determined separately for the right and left knee (maximum score 24 at each side) as well as for the right and left hip (maximum score 17 at each side). A higher final score reflected more severe osteoarthritis.

Disability and physical performance assessment

The ability to perform selected activities of daily living was reported as the need for help or inability to rise from bed/chair, transfer, bathe, dress and use a toilet. Mobility impairment was described by the need for support (cane, wheel chair, furniture) for movement.

The physical activity level was computed using three questions on the frequency of walking 500 m, riding a bike over 1 km and gardening.18 Those who reported never doing these three activities were coded as sedentary, those who engaged in at least two every day or more than once a day were coded as active, and those in between were coded as intermediate. The frequency of going shopping and of performing heavy household chores was recorded, as well as the capacity for lifting 5 kg.

Lower-extremity function was assessed by standardised protocols measuring standing balance, walking speed and the ability to rise from a chair.13 14 19 20 Assessments were carried out in the subjects' homes by trained interviewers.

Patients were assigned five performance scores (from 0 to 4) for each test, with 0 representing the inability to complete the test and 4 the highest level of performance. For tests of standing balance, the subjects were asked to maintain their feet in side-by-side, semitandem and tandem positions for 10 s each. Standing balance was scored as follows: side-by-side standing position for 10 s but semitandem position less than 10 s, score 1; semitandem position for 10 s, but full tandem position less than 2 s, score of 2; full tandem position for 3–9 s, score 3; full tandem position for 10 s, score 4. Subjects were asked to walk twice at the normal pace for 3 or 4 m (depending on space in the participant's house), were timed and the speed calculated (m/s). The fastest walk was scored according to speed quartiles, as follows: 0.57 m/s or less, score 1; 0.58–0.71 m/s, score 2; 0.72–0.82 m/s, score 3; 0.83 m/s or greater, score 4. Subjects were asked to fold their arms across their chests and to stand up from a sitting position once; if they were successful, they were asked to stand up and sit down five times as quickly as possible. Quartiles of the length of time required were used for scoring, as follows: 14.6 s or greater, score 1; 12.0–14.5 s, score 2; 11.9–10.0 s, score 3; and 9.9 s or less, score 4.

A summary performance score was formulated by adding the scores of the standing balance, walking and repeatedly rising from a chair tests. The validity of this scale has been demonstrated previously.13

Socioeconomic status, lifestyle factors and comorbidity

Socioeconomic status and lifestyle factors were self-reported during the interview and were obtained in at least 99% of the participants. The variables selected were: monthly income (<€500, ≥€500), living alone (yes/no) and educational level (cut-off ≥8 years, corresponding to compulsory education). Self-report of the number of falls in the previous year was also determined, defining a fall as ‘unintentional movement to the floor or ground’.21 Comorbidity was defined as the presence of at least one of the following: hypertension, myocardial infarct, chronic heart failure, peripheral arteriopathy, stroke, chronic obstructive broncopneumopathy, Parkinson's disease, osteoporosis, neoplasms and diabetes. The frequency of depression was analysed, using the 30-item geriatric depression scale22 and a 15 or greater cut-off score to indicate depression.

Statistical analysis

The population was divided into two groups: cases with evidence of calcification (chondrocalcinosis) and controls (no chondrocalcinosis). The sex and age-standardised prevalence was estimated using the direct standardisation method performed on the target population structure. Quantitative variables were summarised as means±SD and qualitative variables as frequency distributions. Analysis of variance or the t test was used to compare mean values among groups for normally distributed variables, and the non-parametric Mann–Whitney test was for non-normal variables. The χ2 test was applied to compare categorical distributions. Logistic regression analyses were performed to estimate the age and osteoarthritis severity (expressed by means of the site-specific RFS) adjusted p, OR and 95% CI. For the study of chondrocalcinosis correlation with knee and hip clinical features, left and right limbs were analysed separately. A p level lower than 0.05 was considered significant. All statistical analyses were performed using SAS statistical software package version 8.2.


The characteristics of the total ProVA and x-ray studied populations are reported in table 1. In the latter, the prevalence of chondrocalcinosis was previously reported as 10.4%.5 Subjects with chondrocalcinosis were older and more frequently women. This remained statistically significant after adjustment for age, but not for osteoarthritis. Knee osteoarthritis, classified according to ACR, affected 6.9% of the no chondrocalcinosis and 18.2% of the chondrocalcinosis subjects (age and sex-adjusted p=0.003). Clinical osteoarthritis affected 18.5% of the no chondrocalcinosis and 28.4% of the chondrocalcinosis subjects (age and sex adjusted p=0.05). According to ACR criteria, hip osteoarthritis was found in 11.2% of no chondrocalcinosis versus 10.7% of chondrocalcinosis subjects (p=NS) and was clinically diagnosed in 9.5% of the no chondrocalcinosis and in 10.1% of the chondrocalcinosis subjects (p=NS). A history of either long or short-term pain was not significantly associated with chondrocalcinosis, nor was the use of analgesics. Comorbidity did not differ between the two populations. The association of each comorbid condition with the presence of chondrocalcinosis was analysed separately, and none reached statistical significance (data not shown). The frequency of the socioeconomical variables and depression was not different in the chondrocalcinosis and no chondrocalcinosis subjects, after adjustment for age and sex.

Table 1

Characteristics of the population

Association of chondrocalcinosis with osteoarthritis

Radiographic features

In the chondrocalcinosis group, the mean RFS was 5.1 (median 4.6) and 5.7 (median 5.0) for the left and right knee, respectively. In the no chondrocalcinosis subjects, RFS was lower than in chondrocalcinosis subjects for both left (3.4; median 2.0) and right (3.8; median 2.0) knees, age-adjusted p<0.0001. RFS of the right knee was found to be worse than the left knee in both groups (chondrocalcinosis p=0.01; no chondrocalcinosis p<0.0001). After age adjustment, a marked difference was noted between the sexes, in which the RFS of the right knee was 6.2 versus 4.5 (chondrocalcinosis vs no chondrocalcinosis) in women and 4.6 versus 2.9 in men, respectively, p=0.003 (figure 1). Mean RFS for the left and right hip were 2.6 (median 2.0) and 2.5 (median 2.0), respectively, in chondrocalcinosis, whereas they were 2.3 (median 1.0) and 2.2 (median 1.0), respectively, in no chondrocalcinosis subjects, without a statistically significant difference (data not shown).

Figure 1

Radiological features score (RFS) of the knee in subjects stratified by site, CC status, and gender. Age-adjusted p, CC vs noCC: *p<0.005; #p<0.01; F= females; M= males.

Clinical features

Analysis of the association of chondrocalcinosis with clinical features of osteoarthritis was site specific (table 2). Chondrocalcinosis at the knee was strongly associated with the clinical features of knee osteoarthritis in the bivariate analysis, and most associations remained significant after adjusting for age. After further adjustment for RFS, an association was still shown for deformity and pain. Conversely, no association was found between hip chondrocalcinosis and hip osteoarthritis except for pain at passive movement and at palpation, the latter remaining after adjustment for age but not for RFS.

Table 2

Clinical features at knee and hip level by site-specific chondrocalcinosis status

Association of chondrocalcinosis with physical disability

Physical disability variables were divided into two groups: self-reported disability and performance, and further subdivided, according to the focus of the investigated task (table 3). In the bivariate analysis, chondrocalcinosis was significantly associated with all items, and was still significantly associated with most after adjustment for age (data not shown) and, even after further adjustment for RFS, a significant association remained for impairment in using a toilet, the need for a cane, difficulty walking 500 m, going shopping and repeatedly rising from a chair.

Table 3

Chondrocalcinosis and physical disability


This study, based on clinical and radiographic assessment and on standardised questionnaires and tests, investigated the occurrence of pain and physical disability in chondrocalcinosis. While osteoarthritis ranks among the top 10 causes of disability worldwide, no literature is available concerning the relationship between physical disability and chondrocalcinosis. Pain and physical function are considered the outcome measures of choice for the assessment of disability in patients affected by osteoarthritis.23 24 We demonstrated that chondrocalcinosis, independently of osteoarthritis, contributes to both pain and physical dysfunction.

In agreement with other studies, we observed a strong relationship between chondrocalcinosis and osteoarthritis, in particular knee osteoarthritis, and both increased in prevalence with age.6 8 Notably, the association of chondrocalcinosis with female gender disappeared when corrected for osteoarthritis. A recent meta-analysis on the relationship between CPPD and osteoarthritis suggests that people with osteoarthritis are three times more likely to have CPPD than people without.11 In our study, the presence of chondrocalcinosis was associated with a higher RFS and a higher frequency of knee osteoarthritis by ACR criteria, whereas the clinical features of osteoarthritis were amplified by the concomitant occurrence of chondrocalcinosis. Some authors suggest that chondrocalcinosis acts as a risk factor for knee osteoarthritis progression; in fact, chondrocalcinosis has been used to identify individuals with radiographic osteoarthritis that will evolve radiographically or clinically by developing joint pain and functional impairment.25 Notwithstanding the confounding factor of older age in chondrocalcinosis patients, the association between chondrocalcinosis and clinical indicators of knee osteoarthritis remained statistically significant even after adjustment for age. Further adjustment for RFS revealed chondrocalcinosis to be an independent contributor to knee deformity and pain. Interestingly, chondrocalcinosis was significantly associated with the latter when clinically assessed, but not when self-reported, suggesting that older patients are not able to discriminate pain experiences.26,,28 Deformity, a common sign in osteoarthritis, is a consequence of a more severe disease, usually caused by destruction of joint tissues, such as the cartilage and menisci, bone remodelling, osteophyte formation and ligamentous damage. In this latter case, deformity may be undetectable by radiography, while subsequent joint instability may influence physical performance. It has been shown that the quality of life and disability in osteoarticular diseases are more related to symptoms than to radiographic severity.29 30 Lower extremity joint pain is highly prevalent in older people and represents a significant determinant of their overall health status.31 32

We also demonstrated that individuals with chondrocalcinosis had poorer physical function, according to self-reported disability and performance parameters. After adjustment for age and RFS, a significant association remained for several activities. Performance assessment is closely related to other health status measures. Lower-extremity function predicts the subsequent development of disability mainly because it reflects the effects of numerous factors, which may also include chondrocalcinosis, less likely to determine outright disability per se.13 14

The link between pain and physical impairment in patients with osteoarthritis is well established. Increased symptoms and decreased physical activity can contribute to disability, but little is known about their interrelationships. Previous studies highlighting the association between symptoms and physical functioning in disease states found pain and fatigue to be key contributors to disability in osteoarthritis patients,33 34 and also found that pain and fatigue inhibited physical activity.35,,37 We demonstrated that the presence of chondrocalcinosis represents a further, independent, determinant of decreased activity. While ageing is a major risk and a confounding factor for both osteoarthritis and chondrocalcinosis, in our population, the outcome in terms of pain and disability is clearly maintained after adjustment for age.

The present study has some limitations: acute episodes were only self-reported, and synovial fluid collection and analysis as well as patellofemoral x-ray views were not performed.

The ProVA was an epidemiological survey, thus it was not focused on rheumatic diseases alone and some specific evaluations were avoided to limit invasive procedures. But the study's strengths are found in its epidemiological nature: the large sample size and number of variables allowed a more comprehensive and powerful statistical analysis and the information was objective. As the data were cross-sectional, we were unable to clarify causality. A low-grade local inflammation could be hypothesised, not detectable by systemic markers, as already reported.5

In conclusion, the present study contributes to the understanding of pain and decreased physical function in chondrocalcinosis. Although chondrocalcinosis may be an occasional finding on x-rays, its significance should not be minimised, as chondrocalcinosis is associated with poorer physical function and more symptomatic osteoarthritis. As both frequently occur in older people, the disability they induce may seriously compromise individuals' quality of life and worsen comorbidity.


The authors are grateful to the interviewers, nurses, physicians and statisticians who collaborated in data collection, to the staff of local health units (ASL) nos 15 and 18 of the Veneto region and to all the participants. The authors would also like to thank Mr Peter Rinearson and Ms Linda Inverso for English revision of the manuscript.



  • The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention.

  • Funding The ProVA Study was supported by the Fondazione Cassa di Risparmio di Padova e Rovigo.

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval This study was conducted with the approval of the local ethics committees at the study centres.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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