Background The Italian Society for Orthopaedics and Traumatology conceived this guidance—which is primarily addressed to Italian orthopedic surgeons, but should also prove useful to other bone specialists and to general practitioners—in order to improve the diagnosis, prevention, and treatment of osteoporosis and its consequences.Materials and methodsLiterature reviews by a multidisciplinary team.ResultsThe following topics are covered: the role of instrumental, metabolic, and genetic evaluations in the diagnosis of osteoporosis; appraisal of the risk of fracture and thresholds for intervention; general strategies for the prevention and treatment of osteoporosis (primary and secondary prevention); the pharmacologic treatment of osteoporosis; the setting and implementation of fracture liaison services for tertiary prevention. Grade A, B, and C recommendations are provided based on the main levels of evidence (1–3). Toolboxes for everyday clinical practice are provided.ConclusionsThe first up-to-date Italian guidelines for the primary, secondary, and tertiary prevention of osteoporosis and osteoporotic fractures are presented.

➤ Bone and muscle tissues are in close relationship, and the aging process is a factor involved in the loss of the functionality of both bones and muscles.➤ Sarcopenia and osteoporosis are linked from a biological and functional perspective and are related to an increased fracture risk in the elderly.➤ The increased fracture risk in sarcopenic and osteoporotic subjects is due to the decline of muscle mass and strength, the decrease in bone mineral density, and limited mobility.

The influence of hormones on tendon structure and metabolism needs to be further investigated. If found to be significant, multidisciplinary preventive and therapeutic strategies should then be developed.

Despite the high level achieved in the field of shoulder surgery, a global consensus on rotator cuff tears management is lacking. This work is divided into two main sessions: in the first, we set questions about hot topics involved in the rotator cuff tears, from the etiopathogenesis to the surgical treatment. In the second, we answered these questions by mentioning Evidence Based Medicine. The aim of the present work is to provide easily accessible guidelines: they could be considered as recommendations for a good clinical practice developed through a process of sys- © C I C E d i z i o n i I n t e r n a z i o n a l i tematic review of the literature and expert opinion, in order to improve the quality of care and rationalize the use of resources. KEY WORDS: rotator cuff tears, Guidelines. IntroductionThe pathologies of the rotator cuff are common and they can be considered as a natural decline of the muscletendon unit in aging with statistically significant increase in frequency after 50 years. The painful shoulder is related in 30-70% of cases to disorders of the rotator cuff. The incidence of rotator cuff tears varies between 5 and 40%, although it is very difficult to establish the real incidence of these lesions, which are often asymptomatic. Currently, the pathology of the rotator cuff is considered to be multifactorial, because extrinsic and intrinsic factors play important roles, although it remains unclear the specific weight of each of these factors (Tab. 1). and often increased in number. staining eosinophilic There is a loss of orientation of homogeneous preparation the cores in relation to the bundles with hematoxylin/eosin. of collagen fibers. Chromatin has a dark color. Muscles, Ligaments and Tendons Grade 4 SevereComplete loss of orientation of The cores are reduced in number, Hyalinization with a homogeneous degeneration the collagen fiber bundles.small, dark and round. appearance. I.S.Mu.L.T -Rotator Cuff Tears Guidelines Grade 1The nuclei become more Colorable mucin between Decreased polarization Occasional clusters oval or round in shape fiber bundles but still fibers: separation of the of capillaries, less than without large cytoplasm. discrete number. individual fibers with one per 10 fields at high maintenance of the magnification. demarcation of the beams. Grade 2The nuclei are circular, Colorable mucin between Separation of the fibers 1-2 cluster of capillaries slightly widened and the fibers with loss with loss of demarcation for 10 fields at high a small amount of demarcation and a clear loss of normal magnification. of cytoplasm becomes of the beams. polarization. visible. Grade 3The nuclei are round, Abundant mucin among Demarcated separation More than two clusters wide with abundant poor colorable collagen. of fibers with complete to 10 fields at high cytoplasm and loss of architecture. magnification. the formation of a gap (chondroid change). © C I C E d i z i o n i I n t e r n a z i o n a l i MethodologyThe Authors were divided into four groups: -Coordinator: he conce...

Pentraxin 3 (PTX3) is a multifunctional glycoprotein regulating inflammatory response, cell proliferation and migration and deposition and remodelling of the extracellular matrix by a variety of cells. In this study, we investigated the possible role of PTX3 in bone homeostasis. To this end, we compared the expression and function of PTX3 in human osteoblasts of osteoporotic, osteoarthritic patients and young subjects not affected by bone diseases. Immunohistochemical analysis performed on bone head biopsies showed a close association between bone health and the number of osteoblasts expressing PTX3. Noteworthy, the proportion of PTX3-positive osteoblasts resulted to be significantly lower in osteoporotic patients compared with both young patients and osteoarthritic patients of the same age. Ex vivo culture of osteoblasts isolated from the three groups of patients confirmed in vivo observation. Specifically, we observed rare runt-related transcription factor 2 (RUNX2) immunopositive osteoblasts expressing PTX3 in cell cultures derived from osteoporotic patients and western blotting analysis showed 80% reduction of PTX3 in the corresponding culture extracts compared with young and osteoarthritic patients. The treatment of human osteoblast primary cultures derived from young patients with anti-PTX3 antibody dramatically affected osteoblast behaviour. Indeed, they lost the morphological and molecular features typical of mature osteoblasts, acquiring fibroblast-like shape and highly decreasing nuclear factor kappa-B ligand (RANKL) and RUNX2 expression. Also, the inhibition of PTX3 negatively affected osteoblast proliferation and their ability to form cell clusters and microhydroxyapatite crystals. Altogether, these results suggest a central role of PTX3 in bone homeostasis showing its involvement in osteoblast proliferation, differentiation and function.

Stem cell factor (SCF), the ligand of c-kit, is a key cytokine for hematopoiesis. Hematopoietic precursors express c-kit, whereas differentiated cells of hematopoietic lineage are negative for this receptor, with the exception of NK cells, mast cells, and a few others. While it has long been recognized that dendritic cells (DCs) can express c-kit, several questions remain concerning the SCF/c-kit axis in DCs. This is particularly relevant for DCs found in those organs wherein SCF is highly expressed, including the bone marrow (BM). We characterized c-kit expression by conventional DCs (cDCs) from BM and demonstrated a higher proportion of c-kit+ cells among type 1 cDC subsets (cDC1s) than type 2 cDC subsets (cDC2s) in both humans and mice, whereas similar levels of c-kit expression were observed in cDC1s and cDC2s from mouse spleen. To further study c-kit regulation, DCs were generated with granulocyte-macrophage colony-stimulating factor (GM-CSF) from mouse BM, a widely used protocol. CD11c+ cells were purified from pooled non-adherent and slightly adherent cells collected after 7 days of culture, thus obtaining highly purified BM-derived DCs (BMdDCs). BMdDCs contained a small fraction of c-kit+ cells, and by replating them for 2 days with GM-CSF, we obtained a homogeneous population of c-kit+ CD40hi MHCIIhi cells. Not only did BMdDCs express c-kit but they also produced SCF, and both were striking upregulated if GM-CSF was omitted after replating. Furthermore, a small but significant reduction in BMdDC survival was observed upon SCF silencing. Incubation of BMdDCs with SCF did not modulate antigen presentation ability of these cells, nor it did regulate their membrane expression of the chemokine receptor CXCR4. We conclude that the SCF/c-kit-mediated prosurvival circuit may have been overlooked because of the prominent use of GM-CSF in DC cultures in vitro, including those human DC cultures destined for the clinics. We speculate that DCs more prominently rely on SCF in vivo in some microenvironments, with potential implications for graft-versus-host disease and antitumor immunity.

BackgroundSarcopenia, osteoporosis and osteoarthritis are the most frequent musculoskeletal disorders affecting older people. The main aim of this study was to test the hypothesis that the balance between BMPs and myostatin pathways regulates the age-related muscle degeneration in OP and OA patients. To this end, we investigated the relationship among the expression of BMP-2/4-7, myostatin and phosphorylated Smads1-5-8 and the muscle quality, evaluated in term of fibers atrophy and satellite cells activity.MethodsIn this retrospective study, we collected 123 biopsies of vastus lateralis: 48 biopsies from patients who underwent hip arthroplasty for subcapital fractures of the femur (OP), 55 biopsies from patients who underwent hip arthroplasty for osteoarthritis (OA) and 20 biopsies from patients who underwent hip arthroplasty for high-energy hip fractures (CTRL). Muscle biopsies were fixed in 4% paraformaldehyde and paraffin embedded. Serial sections were used for morphometrical and immunohistochemical analysis (BMP/2/4-7, myostatin, Smads1-5-8, Pax7 and myogenin). In addition, 1 mm3 of muscle tissue of each patient was embedded in epon for ultrastructural study.ResultsMorphometric data indicated an increase of the number of atrophic fibers in OP patients compare to OA. In line with these data, we found an high regenerative potential in muscle tissues of OA patients due to the significant amount of both Pax7 and myogenin positive satellite cells detected in OA group. In addition, our data showed the decrease of BMP2/4 and -7 expression in OP patients compared to both OA group and CTRL. Conversely, OP patients were characterized by high levels of myostatin expression. A different expression profile was also found for phosphorylated Smad1-5-8 between OP and OA patients. In particular, OP patients showed a low number of positive phosphorylated Smad1-5-8 nuclei.ConclusionThe identification of molecular pathways involved in the pathogenesis of sarcopenia open new prospective for the development of drugs able to prevent/treat the muscle impairment that occur in elderly. Results here reported, highlighting the role of BMPs and myostatin pathways in physio-pathogenesis of human sarcopenia, allow us to propose human recombinant BMP-2/7 and anti-myostatin antibodies as a possible therapeutic option for the sarcopenia.

The characterization of molecular mechanisms underlying the bone-muscle crosstalk could open new therapeutic perspectives in elderly diseases.