Calcified cartilage in patients with osteoarthritis of the hip compared to that of healthy subjects. A design-based histological study.

OBJECTIVE: Calcified cartilage is suggested to be involved in the pathogenesis of osteoarthritis (OA) by facilitating endochondral ossification at the bone-cartilage unit. Therefore, the objective was to quantify the volume and surface area of the calcified cartilage in the femoral head in OA patients and healthy subjects. MATERIALS AND METHODS: We used design-based stereological principles, i.e., systematic uniform random sampling and vertical uniform random sections of the entire femoral head. We investigated the articular and calcified cartilage and femoral head surface area and volume, excluding fovea capitis and marginal osteophytes, in 20 patients with OA and 15 healthy subjects. RESULTS: The volume of the calcified cartilage was significantly larger for the patients with OA compared with the healthy subjects (mean difference [95% CI]) (284 [110,457] mm3, p = 0.002). The upper and lower surface area of the calcified cartilage, i.e. the tidemark and cement line, were both significantly larger for OA patients compared with the healthy subjects (17.8 [8.4,27.3] cm2, p < 0.001) and (38.7 [20.8,56.7] cm2, p = 0.002), respectively. The volume of the calcified cartilage and the volume of the femoral head were significantly correlated for the patients with OA (Spearman's ρ = 0.51, p = 0.021), but not for the healthy subjects (ρ = 0.41, p = 0.123). CONCLUSIONS: Patients with OA had a larger femoral head surface area and more calcified cartilage compared to healthy subjects. The volume of the calcified cartilage correlated positively with the volume of the femoral head for patients with OA, but not for healthy subjects. This strongly supports the existing view that bone growth in OA is associated with endochondral ossification.

Histomorphometric case-control study of subarticular osteophytes in patients with osteoarthritis of the hip.

OBJECTIVE: The objective of this cross-sectional case-control study was to determine the prevalence and size of marginal and subarticular osteophytes in patients with osteoarthritis (OA), and to compare these to that of a control group. DESIGN: We investigated femoral heads from 25 patients with OA following hip replacement surgery, and 25 femoral heads from a control group obtained post-mortem. The area and boundary length of the femoral head, marginal osteophytes, and subarticular osteophytes were determined with histomorphometry. Marginal osteophytes were defined histologically as bony projections at the peripheral margin of the femoral head, while subarticular osteophytes were defined as areas of bone that expanded from the normal curvature of the femoral head into the articular cartilage. RESULTS: The prevalence of OA patients with marginal- and subarticular osteophytes were 100 and 84%, respectively. Whereas the prevalence of the participants in the control group with marginal- and subarticular osteophytes were 56 and 28%, respectively. The area and boundary length of marginal osteophytes was (median (Interquartile range)) 165.3mm2 (121.4-254.0) mm2 and 75.1 mm (50.8-99.3) mm for patients with OA compared to 0 mm2 (0-0.5) mm2 and 0 mm (0-0.5) mm for the control group (P <  0.001). For the subarticular osteophytes, the area and boundary length was 1.0 mm2 (0-4.4) mm2 and 1.4 mm (0-6.5) mm for patients with OA compared to 0 mm2 (0-0.5) mm2 and 0 mm (0-0.5) mm for the control group (P <  0.001). CONCLUSION: As expected, both marginal- and subarticular osteophytes at the femoral head, were more frequent and larger in patients with OA than in the control group. However, in the control group, subarticular osteophytes were more prevalent than expected from the minor osteophytic changes at the femoral head margin, which may suggest that subarticular osteophytes are an early degenerative phenomenon that ultimately might develop into clinical osteoarthritis.

Age-related histological changes in calcified cartilage and subchondral bone in femoral heads from healthy humans.

OBJECTIVE: Age is the most important risk factor for osteoarthritis (OA). It is suggested that changes in subchondral bone and calcified cartilage may occur in early OA. Therefore, the aim was to investigate age-related changes in the femoral head composition. We hypothesise that the thickness of the subchondral bone plate decreases with age, while the thickness of the calcified cartilage increases with age as seen in early-stage OA. METHODS: Femoral heads from 29 women (20-74 years) and 32 men (23-78 years), who had died suddenly and unexpectedly, were obtained at autopsy. Individuals with bone or joint diseases or macroscopic abnormal cartilage were excluded. Using design-based stereology, femoral head volume as well as thickness and volume of the calcified cartilage and subchondral bone plate were estimated and correlated to sex and age. RESULTS: The thickness and volume of the subchondral bone plate were not correlated with age. Calcified cartilage thickness and volume correlated positively with age in women, while the femoral head volume was correlated positively with age in men. CONCLUSION: In human femoral heads obtained from a cross-sectional population without macroscopic OA changes, the thickness of the subchondral bone plate did not change with age, which differs from the thinning seen in early OA. Surprisingly, the age-related changes of the volume and thickness of the calcified cartilage and of the volume of the femoral head were different for women and men. This indicate that cartilage and bone metabolism is sex-specific, which may influence ageing of the hip joint.

Thickness of the bone-cartilage unit in relation to osteoarthritis severity in the human hip joint.

OBJECTIVE: Bone formation is a hallmark of osteoarthritis (OA). It has been speculated that bone formation may occur because of ossification at the bone-cartilage unit, that is, bone formation directly involving the calcified cartilage (CC). This study aimed to investigate the thickness of the CC and subchondral bone (SCB) in relation to the severity of the overlying articular cartilage (AC) degeneration. DESIGN: We investigated femoral heads from 20 patients with OA and 15 healthy subjects with design-based stereology using systematic uniform random sampling of the entire joint surface. This was combined with the Osteoarthritis Research Society International (OARSI) OA cartilage histopathology assessment system, thus obtaining focal OARSI grades paired with thickness measurements of AC, CC and the SCB. RESULTS: The patients with OA had thicker CC (mean 159; 95% CI 144 to 177 µm) compared with the healthy subjects (mean 132; 95% CI 113 to 1550 µm; p=0.036), and this difference was even higher in areas without loss of AC thickness (OARSI grade ≤3); 187 (95% CI 164 to 214) µm vs 132 (95% CI 113 to 155) µm (p=0.001). In the patients with OA, a thicker SCB was observed in areas with loss of AC thickness (OARSI grade ≥4), but not in areas without loss of AC thickness (OARSI grade ≤3). CONCLUSION: The study showed that thicker CC is present in early stages of OA, suggesting that bone formation by endochondral ossification is an early phenomenon of OA. Thickening of the SCB was present, but only in areas with denuded bone. Suggesting that also appositional bone growth occurs and that it may be a consequence of changed biomechanics.

[Monitoring renal function in patients treated with cytostatics]. / Måling af nyrefunktion under cytostatisk behandling.

INTRODUCTION: Some cytostatics, used in the treatment of cancer, are excreted by the kidneys and may be nephrotoxic. The glomerular filtration rate (GFR) represents a method for reliable assessement of the 51Cr-EDTA plasma clearance before and during treatment with nephrotoxic drugs. The aim of this retrospective study was to evaluate whether this method could be replaced by a more simplified GFR estimate calculated from the creatinine plasma concentration. MATERIALS AND METHODS: We included all patients who had had at least four GFR measurements in 2005 as part of their nephrotoxic cytostatic treatment. The estimated GFR (eGFR) was calculated from sex, age and weight, according to the Cockcroft formula. RESULTS: Forty-eight patients with a mean age of 47 years were included. 51Cr-EDTA plasma clearance and eGFR showed a poor correlation (r(2) = 0,678). On average, GFR decreased from 95 ml/min to 80 ml/min from the first to the fourth measurement, whereas plasma concentration of creatinine and eGFR remained unchanged. In 13 patients (27%), the treatment dose was reduced due to a fall in GFR. Seven of these 13 patients would have continued their treatment unchanged, if the clinical decision had been based on eGFR. CONCLUSION: Neither creatinine plasma concentration nor estimated GFR ad modum Cockcroft can be recommended for measurement of GFR in patients treated with nephrotoxic cytostatics.

[Rheumatoid arthritis with atlanto-axial subluxation. Pre-and postoperative symptoms, radiological findings and operative complications]. / Reumatoid artritis med atlantoaksial subluksation. Prae- og postoperative symptomer, røntgenfund og operationskomplikationer.

INTRODUCTION: The aim of the study was to study pre- and postoperative symptoms, radiological findings and operative complications in rheumatoid arthritis (RA) patients, operated in the atlantoaxial joint. MATERIALS AND METHODS: A retrospective study of 31 RA patients (24 women, seven men) operated for anterior atlantoaxial subluxation (aAAS) at the Neurosurgical Department, Aarhus University Hospital, in the period of 1993-2003. Information was obtained retrospectively from the patients charge. RESULTS: Mean age at RA debut was 38 years (16-69 yrs), and neck symptoms were seen after a mean time of 15 years (0-39 yrs) of illness. Radiological examination at this time showed irreversible atlantoaxial changes, and operation was performed within 0-9 years (mean 1.6 yrs). The patients were characterized by high disease activity: C-reactive protein, anaemia, positive IgM-rheumatoid factor (84%), and progressive radiological changes in the peripheral joints. All patients were treated with DMARDs (disease modifying anti rheumatic drugs). Neck pain (100%) and neurological symptoms/manifestations (87%) were seen preoperatively. After operation symptoms were relieved in 68% of the patients, while 22% were unchanged, and 10% had worsened. Postoperative complications included cardiac death, dislocation of the cervical spine, fracture of arcus atlantis, hemiparesis, dysphagia, bed sores and infection of the surgical scar (29%). CONCLUSION: Neck symptoms were seen after 15 years of illness, and within the following 1.6 years patients were operated for aAAS. After the operation most of the patients (68%) had relief from symptoms, while 29% had postoperative complications, including cardiac death, dislocation of the cervical spine, fracture of arcus atlantis, hemiparesis, dysphagia, bed sores and infection in the surgical scar.