Bone microstructure and regional distribution of osteoblast and osteoclast activity in the osteonecrotic femoral head.

OBJECTIVE: To detect and compare the bone microstructure and osteoblast and osteoclast activity in different regions of human osteonecrotic femoral heads. METHODS: Osteonecrotic femoral heads were obtained from 10 patients (6 males, 4 females; Ficat IV) undergoing total hip arthroplasty between 2011 and 2013. The samples were divided into subchondral bone, necrotic, sclerotic, and healthy regions based on micro-computed tomography (CT) images. The bone microstructure, micromechanics, and osteoblast and osteoclast activity were assessed using micro-CT, pathology, immunohistochemistry, nanoindentation, reverse transcription polymerase chain reaction (RT-PCR), tartrate-resistant acid phosphatase staining and Western blotting. RESULTS: (1) The spatial structure of the bone trabeculae differed markedly in the various regions of the osteonecrotic femoral heads. (2) The elastic modulus and hardness of the bone trabeculae in the healthy and necrotic regions did not differ significantly (P >0.05). (3) The subchondral bone and necrotic region were positive on TRAP staining, while the other regions were negative. (4) On immunohistochemical staining, RANK and RANKL staining intensities were increased significantly in the subchondral bone and necrotic region compared with the healthy region, while RUNX2 and BMP2 staining intensities were increased significantly in the sclerotic region compared with the necrotic region. (5) OPG, RANK, RANKL, RUNX2, BMP2, and BMP7 protein levels were greater in the necrotic and sclerotic region than in subchondral bone and the healthy region. CONCLUSION: The micromechanical properties of bone trabeculae in the necrotic region did not differ significantly from the healthy region. During the progress of osteonecrosis, the bone structure changed markedly. Osteoclast activity increased in subchondral bone and the necrotic region while osteoblast activity increased in the sclerotic region. We speculate that the altered osteoblast and osteoclast activity leads to a reduction in macroscopic mechanical strength.

Basic research and clinical applications of bisphosphonates in bone disease: what have we learned over the last 40 years?

It is now 40 years since bisphosphonates (BPs) were first used in the clinic. So, it is timely to provide a brief review of what we have learned about these agents in bone disease. BPs are bone-specific and have been classified into two major groups on the basis of their distinct molecular modes of action: amino-BPs and non-amino-BPs. The amino-BPs are more potent and they inhibit farnesyl pyrophosphate synthase (FPPS), a key enzyme of the mavalonate/cholesterol biosynthetic pathway, while the non-amino-BPs inhibit osteoclast activity, by incorporation into non-hydrolyzable analogs of ATP. Both amino-BPs and non-amino-BPs can protect osteoblasts and osteocytes against apoptosis. The BPs are widely used in the clinic to treat various diseases characterized by excessive bone resorption, including osteoporosis, myeloma, bone metastasis, Legg-Perthes disease, malignant hyperparathyroidism, and other conditions featuring bone fragility. This review provides insights into some of the adverse effects of BPs, such as gastric irritation, osteonecrosis of the jaw, atypical femoral fractures, esophageal cancer, atrial fibrillation, and ocular inflammation. In conclusion, this review covers the biochemical and molecular mechanisms of action of BPs in bone, particularly the discovery that BPs have direct anti-apoptotic effects on osteoblasts and osteocytes, and the current situation of BP use in the clinic.

Computer-aided design and custom-made guide in corrective osteotomy for complex femoral deformity.

Preoperative planning of corrective osteotomy with traditional radiography has limitations in regards to determining the ideal osteotomy location and orientation in three-dimensional femoral deformities. Though a successful operation can be planned preoperatively, intraoperative contingencies might adhere to the procedural plan in the performance of operation. To efficiently perform a planned procedure, proposed is a design to implement three-dimensional reconstruction photography, based on computer-tomography (CT) scan. A custom-made guide was designed to navigate the osteotomy as planned, and additionally, a personalized intramedullary nail was used for fixation after osteotomy. Three-dimensional (3D) photography of deformed femur was established based on the CT dataset and transferred into 3D photography processing software for further planning. Osteotomy planes were designed and adjusted at deformity sites to correct the 3D deformities. The methodology of a custom-made osteotomy guide was introduced in femoral corrective osteotomy, for the first time, to navigate the operation as planned. After the virtual osteotomy and reduction of bone segments, the parameters of a custom-made intramedullary nail were measured for manufacturing. Findings Virtual operation in computer shows complete correction of the 3D deformity. The osteotomy guide, obtained by rapid-prototyping techniques, navigates mimicking surgery on rapid-prototyping model of the involved femur as planned. Internal fixation was achieved using the custom-made intramedullary nail. Interpretation three-dimensional visualization introduces an advantage in preoperative planning for corrective osteotomy of 3D femoral deformity, and the custom-made osteotomy guide is crucial to realize such a deliberate plan during the actual procedures. The internal fixator, such as an intramedullary nail, can be modified or personalized for fixation in unique cases.