Multicenter randomized controlled trial comparing early versus late aquatic therapy after total hip or knee arthroplasty.

OBJECTIVE: To evaluate if the timing of aquatic therapy influences clinical outcomes after total knee arthroplasty (TKA) or total hip arthroplasty (THA). DESIGN: Multicenter randomized controlled trial with 3-, 6-, 12-, and 24-month follow-up. SETTING: Two university hospitals, 1 municipal hospital, and 1 rural hospital. PARTICIPANTS: Patients (N=465) undergoing primary THA (n=280) or TKA (n=185): 156 men, 309 women. INTERVENTION: Patients were randomly assigned to receive aquatic therapy (pool exercises aimed at training of proprioception, coordination, and strengthening) after 6 versus 14 days after THA or TKA. MAIN OUTCOME MEASURES: Primary outcome was self-reported physical function as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at 3-, 6-, 12-, and 24-months postoperatively. Results were compared with published thresholds for minimal clinically important improvements. Secondary outcomes included the Medical Outcomes Study 36-Item Short-Form Health Survey, Lequesne-Hip/Knee-Score, WOMAC-pain and stiffness scores, and patient satisfaction. RESULTS: Baseline characteristics of the 2 groups were similar. Analyzing the total study population did not result in statistically significant differences at all follow-ups. However, when performing subanalysis for THA and TKA, opposite effects of early aquatic therapy were seen between TKA and THA. After TKA all WOMAC subscales were superior in the early aquatic therapy group, with effect sizes of WOMAC physical function ranging from .22 to .39. After THA, however, all outcomes were superior in the late aquatic therapy group, with WOMAC effect sizes ranging from .01 to .19. However, the differences between treatment groups of these subanalyses were not statistically significant. CONCLUSIONS: Early start of aquatic therapy had contrary effects after TKA when compared with THA and it influenced clinical outcomes after TKA. Although the treatment differences did not achieve statistically significance, the effect size for early aquatic therapy after TKA had the same magnitude as the effect size of nonsteroidal anti-inflammatory drugs in the treatment of osteoarthritis of the knee. However, the results of this study do not support the use of early aquatic therapy after THA. The timing of physiotherapeutic interventions has to be clearly defined when conducting studies to evaluate the effect of physiotherapeutic interventions after TKA and THA.

17ß-estradiol reduces expression of MMP-1, -3, and -13 in human primary articular chondrocytes from female patients cultured in a three dimensional alginate system.

Clinical observations have suggested a relationship between osteoarthritis and a changed sex-hormone metabolism, especially in menopausal women. This study analyzes the effect of 17ß-estradiol on expression of matrix metalloproteinases-1, -3, -13 (MMP-1, -3, -13) and tissue inhibitors of metalloproteinases-1, -2 (TIMP-1, -2) in articular chondrocytes. An imbalance of matrix metalloproteinases (MMPs) specialized on degradation of articular cartilage matrix over the respective inhibitors of these enzymes (TIMPs) that leads to matrix destruction was postulated in the pathogenesis of osteoarthritis. Primary human articular chondrocytes from patients of both genders were cultured in alginate beads at 5% O(2) to which 10(-11)M-10(-5)M 17ß-estradiol had been added and analyzed by means of immunohistochemistry, immunocytochemistry and real-time RT-PCR. Since articular chondrocytes in vivo are adapted to a low oxygen tension, culture was performed at 5% O(2). Immunohistochemical staining in articular cartilage tissue from patients and immunocytochemical staining in articular chondrocytes cultured in alginate beads was positive for type II collagen, estrogen receptor α, MMP-1, and -13. It was negative for type I collagen, MMP-3, TIMP-1 and -2. Using real-time RT-PCR, it was demonstrated that physiological and supraphysiological doses of 17ß-estradiol suppress mRNA levels of MMP-3 and -13 significantly in articular chondrocytes of female patients. A significant suppressing effect was also seen in MMP-1 mRNA after a high dose of 10(-5)M 17ß-estradiol. Furthermore, high doses of this hormone led to tendentially lower TIMP-1 levels whereas the TIMP-2 mRNA level was not influenced. In male patients, only incubations with high doses (10(-5)M) of 17ß-estradiol were followed by a tendency to suppressed MMP-1 and TIMP-1 levels while TIMP-2 mRNA level was decreased significantly. There was no effect on MMP-13 expression of cells from male patients. Taken together, application of 17ß-estradiol in physiological doses will improve the imbalance between the amounts of MMPs and TIMPs in articular chondrocytes from female patients. Downregulation of TIMP-2 by 17ß-estradiol in male patients would not be articular cartilage protective.

The influence of oxygen and hydrostatic pressure on articular chondrocytes and adherent bone marrow cells in vitro.

Tissue engineering of articular cartilage from chondrocytes or stem cells is considered to be a potential aspect in the treatment of cartilage defects. In order to optimize culture conditions the influence of low oxygen tension (5%) - single or in combination with intermittent hydrostatic pressure (HP: 30/2 min on/off loading; 0.2 MPa) - on the biosynthetic activity (sulfate and proline incorporation) of human osteoarthritic chondrocytes cultured on collagen I/III membranes was investigated. Additionally, chondrogenesis from high density or monolayer cultures of bovine adherent bone marrow cells (aBMC) with and without chondrogenic medium supplements (CM) was analyzed by RT-PCR (mRNA expression of aggrecan and collagen type II). We could show that low oxygen tension increases significantly the biosynthesis of collagen I/III membrane-associated chondrocytes and even higher under co-stimulation with HP. While there is no chondrogenesis in monolayer cultures, CM induces expression of cartilage matrix molecules in high density cultures of aBMC which is even increased under the influence of low oxygen tension. Both, low oxygen tension and HP without CM are alone not sufficient stimuli for chondrogenesis. It can be concluded that low oxygen tension and HP might be useful tools in cartilage tissue engineering and that these physico-chemical factors promote but do not induce chondrogenesis under the given conditions.