Sclerostin does not play a major role in the pathogenesis of skeletal complications in type 2 diabetes mellitus.

In contrast to previously reported elevations in serum sclerostin levels in diabetic patients, the present study shows that the impaired bone microarchitecture and cellular turnover associated with type 2 diabetes mellitus (T2DM)-like conditions in ZDF rats are not correlated with changes in serum and bone sclerostin expression. INTRODUCTION: T2DM is associated with impaired skeletal structure and a higher prevalence of bone fractures. Sclerostin, a negative regulator of bone formation, is elevated in serum of diabetic patients. We aimed to relate changes in bone architecture and cellular activities to sclerostin production in the Zucker diabetic fatty (ZDF) rat. METHODS: Bone density and architecture were measured by micro-CT and bone remodelling by histomorphometry in tibiae and femurs of 14-week-old male ZDF rats and lean Zucker controls (n = 6/group). RESULTS: ZDF rats showed lower trabecular bone mineral density and bone mass compared to controls, due to decreases in bone volume and thickness, along with impaired bone connectivity and cortical bone geometry. Bone remodelling was impaired in diabetic rats, demonstrated by decreased bone formation rate and increased percentage of tartrate-resistant acid phosphatase-positive osteoclastic surfaces. Serum sclerostin levels (ELISA) were higher in ZDF compared to lean rats at 9 weeks (+40 %, p < 0.01), but this difference disappeared as their glucose control deteriorated and by week 14, ZDF rats had lower sclerostin levels than control rats (-44 %, p < 0.0001). Bone sclerostin mRNA (qPCR) and protein (immunohistochemistry) were similar in ZDF, and lean rats at 14 weeks and genotype did not affect the number of empty osteocytic lacunae in cortical and trabecular bone. CONCLUSION: T2DM results in impaired skeletal architecture through altered remodelling pathways, but despite altered serum levels, it does not appear that sclerostin contributes to the deleterious effect of T2DM in rat bone.

"When can I return to driving?": a review of the current literature on returning to driving after lower limb injury or arthroplasty.

Clinicians are often asked by patients, "When can I drive again?" after lower limb injury or surgery. This question is difficult to answer in the absence of any guidelines. This review aims to collate the currently available evidence and discuss the factors that influence the decision to allow a patient to return to driving. Medline, Web of Science, Scopus, and EMBASE were searched using the following terms: 'brake reaction time', 'brake response time', 'braking force', 'brake pedal force', 'resume driving', 'rate of application of force', 'driving after injury', 'joint replacement and driving', and 'fracture and driving'. Of the relevant literature identified, most studies used the brake reaction time and total brake time as the outcome measures. Varying recovery periods were proposed based on the type and severity of injury or surgery. Surveys of the Driver and Vehicle Licensing Agency, the Police, insurance companies in the United Kingdom and Orthopaedic Surgeons offered a variety of opinions. There is currently insufficient evidence for any authoritative body to determine fitness to drive. The lack of guidance could result in patients being withheld from driving for longer than is necessary, or returning to driving while still unsafe.