UNLABELLED: Osteoclasts degrade bone matrix by secretion of hydrochloric acid and proteases. We studied the processes involved in the degradation of the organic matrix of bone in detail and found that lysosomal acidification is involved in this process and that MMPs are capable of degrading the organic matrix in the absence of cathepsin K.

INTRODUCTION: Osteoclasts resorb bone by secretion of acid by the vacuolar H+-adenosine triphosphatase (V-ATPase) and the chloride channel ClC-7, followed by degradation of the matrix, mainly collagen type I, by cathepsin K and possibly by matrix metalloproteinases (MMPs). However, the switch from acidification to proteolysis and the exact roles of both the ion transporters and the proteinases still remain to be studied.

MATERIALS AND METHODS: We isolated CD14+ monocytes from human peripheral blood from either controls or patients with autosomal dominant osteopetrosis type II (ADOII) caused by defective ClC-7 function and cultured them in the presence of RANKL and macrophage-colony stimulating factor (M-CSF) to generate osteoclasts. We decalcified cortical bovine bone slices and studied the osteoclasts with respect to morphology, markers, and degradation of the decalcified matrix in the presence of various inhibitors of osteoclast acidification and proteolysis, using normal calcified bone as a reference.

RESULTS: We found that ADOII osteoclasts not only have reduced resorption of the calcified matrix, but also 40% reduced degradation of the organic phase of bone. We found that both acidification inhibitors and cathepsin K inhibitors reduced degradation of the organic matrix by 40% in normal osteoclasts, but had no effect in the ADOII osteoclasts. Furthermore, we showed that inhibition of MMPs leads to a 70% reduction in the degradation of the organic bone matrix and that MMPs and cathepsin K have additive effects. Finally, we show that osteoclastic MMPs mediate release of the carboxyterminal telopeptide of type I collagen (ICTP) fragment in the absence of cathepsin K activity, and therefore, to some extent, are able to compensate for the loss of cathepsin K activity.

CONCLUSIONS: These data clearly show that osteoclastic acidification of the lysosomes plays a hitherto nonrecognized role in degradation of the organic matrix. Furthermore, these data shed light on the complicated interplay between acidification dependent and independent proteolytic processes, mediated by cathepsin K and the MMPs, respectively.

Daily smokers and heavy drinkers develop two to four times more complications after major as well as minor surgery. Increased postoperative morbidity is probably due to tobacco and alcohol-related organ dysfunctions which are, however, reversible during abstinence. Preoperative smoking cessation intervention for six to eight weeks significantly reduces postoperative complications after knee and hip replacement. Four weeks of preoperative alcohol intervention significantly improves organ functions before surgery, and reduces complications after colorectal surgery. Preoperative prevention programs are cost-effective. In conclusion, according to present evidence the smoking and drinking patient should be identified, informed, and offered preoperative prevention whenever possible.

BACKGROUND: Impulsive forces in the knee joint have been suspected to be a co-factor in the development and progression of knee osteoarthritis. We thus evaluated the impulsive sagittal ground reaction forces (iGRF), shock waves and lower extremity joint kinematics at heel strike during walking in knee osteoarthritis (OA) patients and compared them to those in healthy subjects.

SUBJECTS AND METHODS: We studied 9 OA patients and 10 healthy subjects using three-dimensional gait analyses concentrated on the heel strike. Impulse GRF (iGRF) was measured together with peak accelerations (PA) at the tibial tuberosity and sacrum. Sagittal lower extremity joint angles at heel strike were extracted from the gait analyses. As OA is painful and pain might alter movement strategies, the patient group was also evaluated following pain relief by intraarticular lidocaine injections.

RESULTS: The two groups showed similar iGRF, similar tibial and sacral PA, and similar joint angles at heel strike. Following pain relief, the OA patients struck the ground with more extended hip and knee joints and lower tibial PA compared to the painful condition. Although such changes occurred after pain relief, all parameters were within their normal ranges.

INTERPRETATION: OA patients and healthy subjects show similar impulse-forces and joint kinematics at heel strike. Following pain relief in the patient group, changes in tibial PA and in hip and knee joint angles were observed but these were still within the normal range. Our findings make us question the hypothesis that impulse-forces generated at heel strike during walking contribute to progression of OA.

The aim of this study was to compare long-term recurrence and death rates after a first episode of acute pancreatitis in patients with and without gallstones. Additionally, it was of interest to find out if there were factors predictive of readmission or death.