This study investigates the effects of kyphoplasty on pain and mobility in patients with osteoporosis and painful vertebral fractures compared with conventional medical management.Introduction: Pharmacological treatment of patients with primary osteoporosis does not prevent pain and impaired activity of patients with painful vertebral fractures. Therefore, we evaluated the clinical outcome after kyphoplasty in patients with vertebral fractures and associated chronic pain for >12 months. Materials and Methods: Sixty patients with primary osteoporosis and painful vertebral fractures presenting for >12 months were included in this prospective, nonrandomized controlled study. Twenty-four hours before performing kyphoplasty, the patients self-determined their inclusion into the kyphoplasty or control group so that 40 patients were treated with kyphoplasty, whereas 20 served as controls. This study assessed changes in radiomorphology, pain visual analog scale (VAS) score, daily activities (European Vertebral Osteoporosis Study [EVOS] score), number of new vertebral fractures, and health care use. Outcomes were assessed before treatment and at 3 and 6 months of follow-up. All patients received standard medical treatment (1g calcium, 1000 IE vitamin D 3 , standard dose of oral aminobisphosphonate, pain medication, physical therapy). Results: Kyphoplasty increased midline vertebral height of the treated vertebral bodies by 12.1%, whereas in the control group, vertebral height decreased by 8.2% (p ‫ס‬ 0.001). Augmentation and internal stabilization by kyphoplasty resulted in a reduction of back pain. VAS pain scores improved in the kyphoplasty group from 26.2 ± 2 to 44.2 ± 3.3 (SD; p ‫ס‬ 0.007) and in the control group from 33.6 ± 4.1 to 35.6 ± 4.1 (not significant), whereas the EVOS score increased in the kyphoplasty group from 43.8 ± 2.4 to 54.5 ± 2.7 (p ‫ס‬ 0.031) and in the control group from 39.8 ± 4.5 to 43.8 ± 4.6 (not significant). The number of back pain-related doctor visits within the 6-month follow-up period decreased significantly after kyphoplasty compared with controls: mean of 3.3 visits/patient in the kyphoplasty group and a mean of 8.6 visits/patient in the control group (p ‫ס‬ 0.0147). Conclusions:The results of this study show significantly increased vertebral height, reduced pain, and improved mobility in patients after kyphoplasty. Kyphoplasty performed in appropriately selected osteoporotic patients with painful vertebral fractures is a promising addition to current medical treatment.

Studies on primary osteocytes, which compose >90-95% of bone cells, embedded throughout the mineralized matrix, are a major challenge because of their difficult accessibility and the very rare models available in vitro. We engineered a 3D culture method of primary human osteoblast differentiation into osteocytes. These 3D-differentiated osteocytes were compared with 2D-cultured cells and with human microdissected cortical osteocytes obtained from bone cryosections. Human primary osteoblasts were seeded either within the interspace of calibrated biphasic calcium phosphate particles or on plastic culture dishes and cultured for 4 wk in the absence of differentiation factors. Osteocyte differentiation was assessed by histological and immunohistological analysis after paraffin embedding of culture after various times, as well as by quantitative RT-PCR analysis of a panel of osteoblast and osteocyte markers after nucleic acid extraction. Histological analysis showed, after only 1 wk, the presence of an osteoid matrix including many lacunae in which the cells were individually embedded, exhibiting characteristics of osteocyte-like cells. Real-time PCR expression of a set of bone-related genes confirmed their osteocyte phenotype. Comparison with plasticcultured cells and mature osteocytes microdissected from human cortical bone allowed to assess their maturation stage as osteoid-osteocytes. This model of primary osteocyte differentiation is a new tool to gain insights into the biology of osteocytes. It should be a suitable method to study the osteoblast-osteocyte differentiation pathway, the osteocyte interaction with the other bone cells, and orchestration of bone remodeling transmitted by mechanical loading and shear stress. It should be used in important cancer research areas such as the cross-talk of osteocytes with tumor cells in bone metastasis, because it has been recently shown that gene expression in osteocytes is strongly affected by cancer cells of different origin. It could also be a very efficient tool for drug testing and bone tissue engineering applications.

Prostate and mammary cancer are among the leading cancers diagnosed and the second leading cause of cancer death in men and women, respectively.1 Both cancers show a high propensity to metastasize to bone. Whereas prostate cancer (CaP) elicits predominantly an osteoblast response resulting in osteosclerotic lesions, mammary cancer (CaM) triggers preferentially an osteoclast reaction with bone resorption and consequent osteolytic lesions.2 Osteolytic and osteosclerotic lesions are prone to pathological fractures. A better understanding of the mechanism(s) determining the osteoclast and osteoblast response to cancer metastases is essential for the identification of therapeutic strategies for prevention of pathological bone fractures in cancer patients.Several factors stimulating osteoblast proliferation and differentiation in a paracrine manner have been shown to be released by CaP and CaM cells in the bone microenvironment and have been postulated to mediate osteoblast response in bone metastasis. 3,4 Factors that modulate proliferation and differentiation can act directly on the osteoblast progenitors or indirectly by activation of factors involved in their generation. 4 Paradigmatic molecules regulating directly osteoblast generation are the bone morphogenetic proteins (BMPs).5 BMPs were first identified by their ability to induce ectopic chondro-osteogenesis in vivo. 6 They play a crucial role in skeletal and joint morphogenesis, bone