Genetic mutations that disrupt osteoblast function can result in skeletal dysmorphogenesis or, more rarely, in increased postnatal bone formation. Here we show that Schnurri-3 (Shn3), a mammalian homolog of the Drosophila zinc finger adapter protein Shn, is an essential regulator of adult bone formation. Mice lacking Shn3 display adult-onset osteosclerosis with increased bone mass due to augmented osteoblast activity. Shn3 was found to control protein levels of Runx2, the principal transcriptional regulator of osteoblast differentiation, by promoting its degradation through recruitment of the E3 ubiquitin ligase WWP1 to Runx2. By this means, Runx2-mediated extracellular matrix mineralization was antagonized, revealing an essential role for Shn3 as a central regulator of postnatal bone mass.

Trace elements are chemical elements in minute quantities, which are known to accumulate in the bone. Cortical and trabecular bones consist of bone structural units (BSUs) such as osteons and bone packets of different mineral content and are separated by cement lines. Previous studies investigating trace elements in bone lacked resolution and therefore very little is known about the local concentration of zinc (Zn), strontium (Sr) and lead (Pb) in BSUs of human bone. We used synchrotron radiation induced micro X-ray fluorescence analysis (SR μ-XRF) in combination with quantitative backscattered electron imaging (qBEI) to determine the distribution and accumulation of Zn, Sr, and Pb in human bone tissue. Fourteen human bone samples (10 femoral necks and 4 femoral heads) from individuals with osteoporotic femoral neck fractures as well as from healthy individuals were analyzed. Fluorescence intensity maps were matched with BE images and correlated with calcium (Ca) content. We found that Zn and Pb had significantly increased levels in the cement lines of all samples compared to the surrounding mineralized bone matrix. Pb and Sr levels were found to be correlated with the degree of mineralization. Interestingly, Zn intensities had no correlation with Ca levels. We have shown for the first time that there is a differential accumulation of the trace elements Zn, Pb and Sr in BSUs of human bone indicating different mechanisms of accumulation.

Ankle arthrodesis (AAD) and total ankle replacement (TAR) are the major surgical treatment options for severe ankle arthritis. There is an ongoing discussion in the orthopaedic community whether ankle arthrodesis or ankle fusion should be the treatment of choice for end stage osteoarthritis. The purpose of this study was to compare the participation in sports and recreational activities in patients who underwent either AAD or TAR for end-stage osteoarthritis of the ankle. A total of 41 patients (21 ankle arthrodesis /20 TAR) were examined at 34.5 (SD18.0) months after surgery. At follow-up, pre- and postoperative participation in sports and recreational activities has been assessed. Activity levels were determined using the ankle activity score according to Halasi et al. and the University of California at Los Angeles (UCLA) activity scale. Clinical and functional outcome was assessed using the American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot score. The percentage of patients participating in sports and recreational activities, UCLA score and AOFAS score were compared between both treatment groups. In the AAD group 86% were active in sports preoperatively and in the TAR group this number was 76%. Postoperatively in both groups 76% were active in sports (AAD, p = 0.08). The UCLA score was 7.0 (± 1.9) in the AAD group and 6.8 (± 1.8) in the TAR group (p = 0.78). The AOFAS score reached 75.6 (± 14) in the AAD group and 75.6 (± 16) in the TAR group (p = 0.97). The ankle activity score decrease was statistically significant for both groups (p = 0.047). Our study revealed no significant difference between the groups concerning activity levels, participation in sports activities, UCLA and AOFAS score. After AAD the number of patients participating in sports decreased. However, this change was not statistically significant.

Long-term effects of risedronate on bone mineralization density distribution in triple transiliac crest biopsies of osteoporotic women were evaluated. In this double-blinded study, 3- and 5-year treatment with risedronate increased the degree and homogeneity of mineralization without producing hypermineralization. These changes at the material level of bone could contribute to risedronate's antifracture efficacy. Introduction: Risedronate, a nitrogen-containing bisphosphonate, is widely used in the treatment of osteoporosis. It reduces bone turnover, increases BMD, and decreases fracture risk. To date, there are no data available on the long-term effects of risedronate on bone mineralization density distribution (BMDD) in humans. Materials and Methods: Osteoporotic women enrolled in the VERT-NA trial received either risedronate (5 mg/day, orally) or placebo for up to 5 years. All subjects received calcium and vitamin D supplementation if deficient at baseline. Triple iliac crest biopsies were collected from a subset of these subjects at baseline and 3 and 5 years. BMDD was measured in these biopsies using quantitative backscattered electron imaging, and the data were also compared with a normal reference group. Results: At baseline, both risedronate and placebo groups had a lower degree and a greater heterogeneity of mineralization as well as an increase in low mineralized bone compared with the normal reference group. The degree of mineralization increased significantly in the risedronate as well as in the placebo group after 3- and 5-year treatment compared with baseline. However, the degree of mineralization did not exceed that of normal. Three-year treatment with risedronate significantly increased the homogeneity of mineralization and slightly decreased low mineralized bone compared with placebo. Surprisingly with 5-year risedronate treatment, heterogeneity of mineralization increased compared with 3-year treatment, which might indicate an increase in newly formed bone. Conclusions: Long-term treatment with risedronate affects the homogeneity and degree of mineralization without inducing hypermineralization of the bone matrix. These changes at the material level of the bone matrix may contribute to risedronate's antifracture efficacy in osteoporotic patients.

Primary bone or soft tissue tumors of the femur sometimes present with severe and extensive bone destruction, leaving few limb-salvage options other than total femur replacement. However, there are few data available regarding total femur replacement and, in particular, regarding implant failures. We asked: (1) What are the revision-free and overall implant survival rates of conventional total femur replacements in patients treated for sarcoma of the femur or soft tissues? (2) What are the revision-free and overall implant survival rates of expandable total femur replacements in skeletally immature patients? (3) Using the comprehensive International Society of Limb Salvage failure-mode classification, what types of complications occur with conventional and expandable total femur replacements? Our retrospective, single-center cohort study was based on data prospectively collected for 50 patients who received a total femur replacement after tumor resection for indications other than carcinoma or metastatic disease. Of the 50 patients, six (12%) were lost to followup before 6 months. Ten of the remaining 44 patients received expandable implants. The mean followup was 57 months (range, 1–280 months) and 172 months (range, 43–289 months) for patients who underwent conventional and expandable total femur replacements, respectively. For implant survival, competing risk analyses were used. At 5 years, revision-free implant survival of conventional total femur replacements was 48% (95% CI, 0.37–0.73), and overall implant survival was 97% (95% CI, 0.004–0.20). Five-year revision-free implant survival of expandable total femur replacements was 30% (95% CI, 0.47–1.00) and overall implant survival was 100%. With conventional total femur replacements soft tissue failures occurred in 13 of 34 patients, structural failures in three, infection in six, and local tumor progression in one. No patient had aseptic loosening with conventional total femur replacements, but hip disarticulation occurred in two patients owing to extensive wound-healing problems and infection. With expandable total femur replacements soft tissue failure, aseptic loosening, and infection occurred in one patient each of 10, and structural failures in three of 10 (two periprosthetic fractures, one loosening of an enhanced tendon anchor). No hip disarticulations were performed. Additionally expandable total femur replacement-related failures included hip instability in eight of 10 patients, contractures attributable to massive scar tissue in six, and defect of the implant’s expansion mechanism in four patients. Although the indications for total femoral resection are rare, we think that total femur replacement is a reasonable treatment option for reconstruction of massive femoral bone defects after tumor resection in adults and skeletally immature patients, and results in limb salvage in most patients. Level IV, therapeutic study.