Fractures to the base of the fifth metatarsal are common, but their treatment remains controversial. Especially for Lawrence and Botte (L&B) type II fractures, there is conflicting evidence and consequently no consensus. Further, many authors consider displacement, articular involvement, and number of fragments an indication for surgery, although evidence is missing. The aim of this study was to evaluate the outcome of functional treatment for all L&B type I and II fractures. Of special interest were the influence of (1) the fracture location (L&B type I vs. II) and (2) the fracture characteristics (displacement, intra-articular involvement, communition) on the subjective outcome. Retrospective registry study with a prospective follow-up. Patients with an acute, isolated, epi-metaphyseal fracture to the fifth metatarsal bone (L&B type I and II) treated by full weightbearing with a minimum follow-up of 6 months were included. Fracture location (L&B type I and II) and characteristics (displacement 2 mm, intra-articular involvement, and number of fragments) were assessed. Outcome parameters were return to work, return to sports, VAS-FA, and SF-12. The influence of the fracture (1) location and (2) -characteristics on these parameters was tested. Thirty-nine patients (40 ± 15 years, 56% female) were enrolled with a mean follow-up of 22 ± 10 months. L&B type I fractures occurred in 59%, type II in 41%. Thirty-one percent of all fractures were dislocated, 74% intra-articular, and 41% multi-fragmentary. Patients returned to work after 17 ± 12 days, to sports after 53 ± 22 days. The VAS-FA score at the final follow-up was 96 ± 4, SF-12 PCS score 57 ± 5 and MCS score 51 ± 8. No complications were reported, no patient required surgery. None of the assessed outcome parameters differed significantly between (1) the different fracture locations (L&B type I vs. II) or (2) the different fracture characteristics (displacement, intra-articular involvement, and number of fragments). (1) Both, L&B I and II fractures featured excellent results with immediate full weightbearing. Consequently, L&B type I and II fractures should be summarized as epi-metaphyseal fractures. (2) Fracture displacement, articular involvement, and number of fragments did not influence the outcome. Therefore, functional treatment should be recommended for all epi-metaphyseal fractures.

Matrilins (MATN1, MATN2, MATN3 and MATN4) are adaptor proteins of the cartilage extracellular matrix (ECM), which bridge the collagen II and proteoglycan networks. In humans, dominant-negative mutations in MATN3 lead to various forms of mild chondrodysplasias. However, single or double matrilin knockout mice generated previously in our laboratory do not show an overt skeletal phenotype, suggesting compensation among the matrilin family members. The aim of our study was to establish a mouse line, which lacks all four matrilins and analyze the consequence of matrilin deficiency on endochondral bone formation and cartilage function. Matn1-4^−/− mice were viable and fertile, and showed a lumbosacral transition phenotype characterized by the sacralization of the sixth lumbar vertebra. The development of the appendicular skeleton, the structure of the growth plate, chondrocyte differentiation, proliferation, and survival were normal in mutant mice. Biochemical analysis of knee cartilage demonstrated moderate alterations in the extractability of the binding partners of matrilins in Matn1-4^−/− mice. Atomic force microscopy (AFM) revealed comparable compressive stiffness but higher collagen fiber diameters in the growth plate cartilage of quadruple mutant compared to wild-type mice. Importantly, Matn1-4^−/− mice developed more severe spontaneous osteoarthritis at the age of 18 months, which was accompanied by changes in the biomechanical properties of the articular cartilage. Interestingly, Matn4^−/− mice also developed age-associated osteoarthritis suggesting a crucial role of MATN4 in maintaining the stability of the articular cartilage. Collectively, our data provide evidence that matrilins are important to protect articular cartilage from deterioration and are involved in the specification of the vertebral column.

Fractures to the osteoporotic bone feature a delay in callus formation and reduced enchondral ossification. Human mesenchymal stem cells (hMSC), the cellular source of fracture healing, are recruited to the fracture site by cytokines, such as BMP-2 and BMP-7. Aim of the study was to scrutinize hMSC for osteoporosis associated alterations in BMP mediated migration and invasion as well as in extracellular matrix (ECM) binding integrin expression. HMSC were isolated from 18 healthy or osteoporotic donors. Migration was assessed using a collagen IV coated micro-slide linear gradient chamber and time-lapse microscopy. Invasion was analyzed utilizing an ECM coated transmembrane invasion assay. Quantitative real-time RT PCR was performed for the ECM binding integrins α1, α2, α3, α4, α5, α11, αv and β1. HMSC from osteoporotic patients showed a significant increase of migration upon BMP-2 or FCS stimulation, as well as a significant increase of invasion upon BMP-2, BMP-7 or FCS stimulation. Nevertheless, the migration and invasion capacity was significantly decreased compared to healthy controls. Out of all integrins analyzed, collagen binding integrin α2 was significantly downregulated in hMSC from osteoporotic patients. In conclusion, we here demonstrate for the first time osteoporosis associated alterations in BMP mediated hMSC recruitment. These findings may underlie the reduced healing of osteoporotic fractures. Nevertheless, the maintained migration and invasion response upon BMP stimulation illustrates the therapeutic potential of these clinically approved substances in the treatment of osteoporotic fractures. Another therapeutic target may be the downregulation of the collagen binding integrin α2 in hMSC from osteoporotic patients.