The hormone calcitonin (CT) is primarily known for its pharmacologic action as an inhibitor of bone resorption, yet CT-deficient mice display increased bone formation. These findings raised the question about the underlying cellular and molecular mechanism of CT action. Here we show that either ubiquitous or osteoclast-specific inactivation of the murine CT receptor (CTR) causes increased bone formation. CT negatively regulates the osteoclast expression of Spns2 gene, which encodes a transporter for the signalling lipid sphingosine 1-phosphate (S1P). CTR-deficient mice show increased S1P levels, and their skeletal phenotype is normalized by deletion of the S1P receptor S1P₃. Finally, pharmacologic treatment with the nonselective S1P receptor agonist FTY720 causes increased bone formation in wild-type, but not in S1P₃-deficient mice. This study redefines the role of CT in skeletal biology, confirms that S1P acts as an osteoanabolic molecule in vivo and provides evidence for a pharmacologically exploitable crosstalk between osteoclasts and osteoblasts.

Background: Nonoperative treatment of stable juvenile osteochondritis dissecans (JOCD) lesions of the knee fails in up to 50% of cases. Healing predictors are needed to identify potential failures and thus determine treatment options. Purpose: A predictive model for healing potential after 6 and 12 months of nonoperative treatment of stable JOCD lesions based on sensitive magnetic resonance imagining (MRI) follow-up measurements was developed. Study Design: Cohort study (diagnosis); Level of evidence, 2. Methods: A retrospective cross-sectional study was conducted to analyze 62 white patients (76 stable JOCD lesions) who were initially treated by restriction of activity until they were free of pain. The primary end point was healing investigated on MRI with follow-up measurements after 6 and 12 months of nonoperative treatment. Multivariate logistic regression was used to determine the influence of age, sex, JOCD lesion size, clinical symptoms, and the occurrence of cystlike lesions (CLLs) on healing potential. Additionally, optimal prognostic cutoffs were defined to differentiate failures from nonfailures. Results: After 6 months of nonoperative treatment, 51 (67%) of 76 stable JOCD lesions showed no progression toward healing or showed signs of instability. Normalized lesion width and area and CLL occurrence differed significantly between failures and nonfailures ( P < .05). A multivariate logistic regression best-predictors model that included age, CLL size, and normalized lesion width best predicted healing after 6 months and resulted in an area under the curve (AUC) of 0.779 ( P < .001). A cutoff at 48% healing probability, as predicted by a nomogram based on age, normalized lesion width, and CLL size, differentiated failures from nonfailures (sensitivity, 60.0%; specificity, 83.7%). After 12 months, 37 lesions (49%) had progressed toward healing, and the sole observation of CLL size had the highest predictive validity (AUC, 0.766). The optimal cutoff was a healing probability of 61% (lesion size, 1.3 mm; sensitivity, 70.3%; specificity, 74.1%). Conclusion: A 6-month period of nonoperative treatment with or without casting might be appropriate if the healing potential is >48%. A 12-month period of nonoperative treatment may be successful if the CLL is <1.3 mm in length as assessed on MRI.

Objective: To analyze the anatomic accuracy of fracture reduction controlled by fluoroscopy as compared with arthroscopically assisted reduction (“fracturoscopy”) in patients with complex tibial plateau fractures (AO/OTA 41-C). Quality of fracturoscopy-guided reduction was checked with postoperative computed tomography. Design: Prospective observational study. Setting: Urban level 1 trauma center. Patients: Seventeen consecutive patients, with a complex, bicondylar tibial plateau fracture. Intervention: The intraoperative, open insertion of an arthroscope (2.4-mm or 2.8-mm optics), to visualize the articular surface and fracture reduction. Main Outcome Measurements: Ability to detect residual fracture depression or gap after previous open reduction under fluoroscopic guidance. Results: An open fracture reduction with fluoroscopic guidance was performed in all cases. In 7 cases, open reduction and fluoroscopy resulted in satisfactory fracture reduction (fluoroscopy group). In 10 of 17 cases, subsequent “fracturoscopy” showed persistent fracture depression (≥2 mm, fracturoscopy group) with the need for intraoperative correction. Patients in the fracturoscopy group demonstrated significantly greater preoperative fragment depression (12.55 ± 6.56 mm) and a larger preoperative fracture gap (7.83 ± 5.49 mm) compared with patients with a satisfactory reduction under fluoroscopy (depression 4.97 ± 4.02 mm, P = 0.016; gap 2.47 ± 1.07 mm, P = 0.023). Fluoroscopy was not successful in achieving satisfactory reduction in cases in which the postero-latero-central region was affected (P = 0.004, χ² test). Postoperative computed tomography demonstrated satisfactory articular reconstruction in all cases. Conclusions: Intraoperative fracturoscopy permitted a significantly improved visualization of fracture fragment displacement, specifically in the postero-latero-central region of the tibial plateau, as compared with fluoroscopy. Fracturoscopy is recommended for fractures involving the postero-latero-central region of the tibial plateau. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Bisphosphonates are a common treatment to reduce osteoporotic fractures. This treatment induces osseous structural and compositional changes accompanied by positive effects on osteoblasts and osteocytes. Here, we test the hypothesis that restored osseous cell behavior, which resembles characteristics of younger, healthy cortical bone, leads to improved bone quality. Microarchitecture and mechanical properties of young, treatment-naïve osteoporosis and bisphosphonate-treated cases were investigated in femoral cortices. Tissue strength was measured using three-point bending. Collagen fibril-level deformation was assessed in non-traumatic and traumatic fracture states using synchrotron small-angle x-ray scattering (SAXS) at low and high strain rates. The lower modulus, strength and fibril deformation measured at low strain rates reflects susceptibility for osteoporotic low-energy fragility fractures. Independent of age, disease and treatment status, SAXS revealed reduced fibril plasticity at high strain rates, characteristic of traumatic fracture. The significantly reduced mechanical integrity in osteoporosis may originate from porosity and alterations to the intra/extrafibrillar structure, while the fibril deformation under treatment indicates improved nano-scale characteristics. In conclusion, losses in strength and fibril deformation at low strain rates correlate with the occurrence of fragility fractures in osteoporosis, while improvements in structural and mechanical properties following bisphosphonate treatment may foster resistance to fracture during physiological strain rates.