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Objective: Fragility fractures (FF) resulting from osteoporosis pose a significant public health challenge in Italy, with considerable socio-health and economic implications. Despite the availability of safe and effective drugs, osteoporosis remains underdiagnosed and undertreated, leaving over 2 million high-risk Italian women without treatment. This paper aims to identify and propose key improvements in the management of osteoporosis, focusing particularly on the critical issues related to the use of anabolic drugs in secondary prevention, according to the current Italian Medicines Agency (AIFA) Note 79., Methods: The Expert Panel, composed of nine recognized Italian experts in rheumatology, analyzed current practices, prescribing criteria, and the most recent literature. Three main reasons for revising the indications on pharmacological treatment of osteoporosis were identified: inadequate treatment of osteoporosis, new evidence regarding frontline placement of anabolics in high-risk conditions, and emerging sequential or combined strategies., Results: The proposed improvements include the adoption of the Derived Fracture Risk Assessment algorithm for accurate fracture risk assessment, revision of AIFA Note 79 to reflect current evidence, improved prescribing appropriateness, broader access to anabolic agents, and the provision of sequential therapies with antiresorptives for teriparatide. These changes aim to enhance patient outcomes, streamline healthcare processes, and address the high percentage of undertreated individuals., Conclusions: This expert opinion emphasizes the importance of the appropriate use of anabolic drugs to reduce FF and associated costs while ensuring the sustainability of the National Health Service. The proposed recommendations are in line with the latest scientific evidence, providing a comprehensive strategy to optimize the management of osteoporosis in Italy. On behalf of the Study Group on Osteoporosis and Skeletal Metabolic Diseases of the Italian Society of Rheumatology.

The mechanisms underlying the development of bone damage in the context of spondyloarthritis (SpA) are not completely understood. To date, a considerable amount of evidence indicates that several developmental pathways are crucially involved in osteoimmunology. The present review explores the biological mechanisms underlying the relationship between inflammatory dysregulation, structural progression, and osteoporosis in this diverse family of conditions. We summarize the current knowledge of bone biology and balance and the foundations of bone regulation, including bone morphogenetic protein, the Wnt pathway, and Hedgehog signaling, as well as the role of cytokines in the development of bone damage in SpA. Other areas surveyed include the pathobiology of bone damage and systemic bone loss (osteoporosis) in SpA and the effects of pharmacological treatment on focal bone damage. Lastly, we present data relative to a survey of bone metabolic assessment in SpA from Italian bone specialist rheumatology centers. The results confirm that most of the attention to bone health is given to postmenopausal subjects and that the aspect of metabolic bone health may still be underrepresented. In our opinion, it may be the time for a call to action to increase the interest in and focus on the diagnosis and management of SpA.

Numerous rheumatic diseases, including rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, systemic lupus erythematosus, systemic sclerosis, dermatomyositis/polymyositis and vasculitis are characterized by osteoporosis and fragility fractures. Inflammatory cytokines, glucocorticoid treatment, immobilization and reduced physical activity due to painful joints and muscle weakness are considered the main risk factors that cause low body mass density values in these diseases. Emerging evidence highlights the role of inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1, IL-6, IL-7 and IL-17, in the regulation of the bone homeostasis. In fact, chronic inflammation is often characterized by an imbalance between bone formation and bone resorption with a net prevalence of osteoclastogenesis, which is an important determinant of bone loss in rheumatic diseases.

In recent years studies have emphasized the importance of glucocorticoid-induced osteoporosis as the second most common form of osteoporosis after postmenopausal osteoporosis. Several studies have underlined that glucocorticoids are responsible for decreasing bone mineral density and increasing bone fragility, resulting in a large increase in fracture risk. This review wants to provide a background regarding the fracture risk of patients exposed to glucocorticoid treatment, considering the fracture risk as the most appropriate parameter to valuate glucocorticoid-induced osteoporosis. In fact, glucocorticoid treatment induces bone loss and increases fracture risk above all affecting trabecular bone, probably through an alteration in bone turnover and microarchitectural changes responsible for an early increased fracture risk which is primary influenced by dose and duration of treatment, body mass index, age and female gender.

Transfusion program and chelating therapy treatment has extended the life expectancy of thalassaemic patient; osteoporosis is considered an important cause of morbidity in adult patients who display increased fracture risk. This is a case report is about a thalassaemic young female with multiple spine fractures (D11, D12 e L2) and lumbar spine DEXA - T score = -3,1 and femoral = -3,4. This was in spite of therapy with alendronate 70 mg/week from January 2006 to September 2007. The patient was subsequentently treated for 18 months with 1-34 recombinant human parathyroid hormone and colecalciferol (100.000 U/monthly). After 4 months of therapy, the patient showed a decrease in spinal pain (Roland and Morris Disability Questionnaire) and an improvement of quality of life (Qualeffo) with normalization of osteocalcin and 25-OHcolecalciferol haematic levels after 6 months. Lumbar spine and femoral DEXA - Tscore, at 18 months, rose respectively to -2,5 and -2,4. Thalassaemia-induced osteoporosis is multifactorial and its management is very difficult. Bone marrow expansion, endocrine dysfunction, iron overload and genetic factors all seem to play important roles in the development of low bone mass in these patients. Bisphosfonates have been used in the management of thalassemia induced osteoporosis but there is no data about fracture risk. Anabolic therapy for thalassemic patients requests additional study on a large scale.

In order to examine the effects of vitamin D on osteoblast function and to evaluate if osteoporotic and normal osteoblasts show a different behaviour in response to vitamin D, this report investigates the changes in osteocalcin production, after 1,25-dihydroxy-vitamin D(3) stimulation of cultured osteoblasts derived from osteoporotic patients. Our results indicate an inadequate osteoblastic function in osteoporosis and demostrate that 1,25-dihydroxy-vitamin D(3) can stimulate the metabolic activity of human osteoblasts in vitro. Considering that osteoporotic bone samples were representative of senile osteoporosis, our results may indicate a different metabolic phenotype in osteoporotic osteoblasts compared with normal osteoblasts. The increased osteocalcin production after 1,25-dihydroxy-vitamin D(3) stimulation of osteoporotic osteoblasts suggests a reduced, but not absent, anabolic function in senile osteoporotic osteoblasts. The results of this study confirm the validity of vitamin D(3) to treat senile osteoporosis and suggest the need of higher vitamin D(3) intake in senile osteoporotic patients than in younger subjects.

Osteoporosis is a condition in which an imbalance appears between bone resorption and formation, with bone resorption exceeding formation. However since the rate of bone loss varies significantly from one individual to another resulting in different degrees of osteoporosis, new biochemical techniques to measure products of bone resorption and bone formation have been used in the last years allowing us to evaluate the degree of bone turnover. Bone tissue is constituted of an inorganic component and an organic matrix of collagen and noncollagenous proteins. Suitable bone marker should report the formation and degradation of all these constituents. Today markers of bone formation and markers of bone resorption are available. According to recent literature and personal data assessment of bone metabolism by the specific biochemical markers is helpful to select osteoporotic patients with high or low bone turnover and these parameters should be used to evaluate whether bone remains sensitive to different therapies.

beta 2-Microglobulin (beta 2m) is a small polypeptide of 99 amino acids with a molecular weight of 11.800. It is found in serum, on the surface of almost all mammalian cells and is part of the surface antigen of the cell membrane of human lymphocytes. Moreover, the heavy chain of major histocompatibility complex class I molecules normally associates in the membrane with beta 2m. According to Canalis, et al this polypeptide is a bone derived growth factor. In our study, serum beta 2m, osteocalcin bone Gla-protein (BGP) and calcium phosphorous metabolism were evaluated in a group of 18 osteoporotic women. Nine were treated with an anabolic steroid, DecaDurabolin and 9 with salmon calcitonin (sCT) for 3 months. The same variables were evaluated in a control group (6 osteoporotic women) treated with oral Ca (1,500 mg/day for 3 months). A significant increase in serum beta 2m and BGP (p < 0.001) was observed after anabolic steroid while a significant decrease in serum beta 2m and BGP (p < 0.01) was observed after sCT. No significant variation for serum beta 2m and BGP was observed in the control group. No significant variation of calcium-phosphorous metabolism was observed in either the control group or the treated group. BGP variations suggest that anabolic steroid stimulates bone formation while a decrease in BGP observed after sCT suggests that this hormone depresses bone turnover via a block in osteoclast activity. Moreover it could be suggested that anabolic steroid and sCT affect beta 2m producing cells.

With the aim of evaluating the role of 1,25 dihydroxyvitamin D in the pathogenesis of osteoporosis, this hormone was studied in 90 subjects. They were divided into three groups: the first group consisted of 30 normal female subjects (aged 30 to 45); the second group comprised 30 elderly female subjects (aged 67 to 90) the third group consisted of female patients (aged 65 to 87) with clinical and radiological evidence of osteoporosis. Variations of serum 1,25 dihydroxyvitamin D, after stimulation with oral P04 (1,000 mg/day for 10 days) and stimulation with oral Ca (1,000 mg/day for 10 days), were studied in 16 osteoporotic females (10 of them received P04) and six Ca (Controls). This second study was performed to evaluate the renal 1-alpha-hydroxylation. No significant variation between serum 1,25 dihydroxyvitamin D of elderly and osteoporotic females was observed when compared with normal young healthy subjects. Moreover, a significant increase in serum 1,25(OH)2D after oral P04 was found in accordance with a significant increase in serum parathormone. These data demonstrate that changes in serum 1,25(OH)2D levels did not seem to play a significant part in the pathogenesis of osteoporosis in our population neither could a deficit of renal 1-alpha-hydroxylation be demonstrated.

Unlabelled: The authors, using the experimental pattern of bone rarefaction induced by a low calcium diet, tried to determine if 25-hydroxycholecalciferol, administered at doses and according to procedures similar to those used in osteoporosis, might interfere in such a process of rarefaction. The statistical evaluation of the results concerning the size of the amount of spongy bone presented evidence for the sharp decrease in the specific bone volume in rats placed on a low calcium diet as compared to control rats. Such a difference is found even between rats treated with 25-OH-D3. Nonetheless, the authors reported a difference--although not statistically significant--that indicated an increase in the amount of bone in rats on a normal diet but treated with vitamin D as compared to control rats., In Conclusion: 25-OH-D3 by itself, the diet being the same, was not able to ameliorate the amount of bone.

Prevention of the experimental bone rarefaction which occurs in rats put on a low calcium diet was attempted by using salmon calcitonin and 25 hydroxyvitamin D given with a similar regimen to that used in human disease. Results were compared with the previously reported effects of synthetic anabolic steroids. Statistical analysis was carried out on measurements of cancellous bone mass. No statistically significant increase in the femoral trabecular bone volume occurred in rats put on an hypocalcemic diet plus treatment by calcitonin and vitamin D whereas such an increase had been noted when anabolic steroids were used. Measurement of the trabecular bone volume of proximal and distal epiphyses demonstrated a statistically significant difference between rats on a hypocalcemic diet treated by 25-OH-D3 and rats treated by calcitonin or controls on a normal diet. In rats on a normal diet, 25 hydroxyvitamin D led to an increase in bone mass which did not reach statistical significance but is probably explained by improvement in calcium intestinal absorption.

A study of femur and wrist fracture prevalence in a large population of Apulia was carried out. These kinds of fractures are closely related to osteoporosis in post-menopausal women and in the elderly, suggesting that a survey of their prevalence in the population could demonstrate the prevalence of osteoporosis itself. In this study a high prevalence of total fractures in young men was demonstrated. The same prevalence was observed for wrist fractures, while femur fractures showed a high prevalence in the young and in men aged 60 to 90 years. In women a high prevalence in the first decades of life was observed for both wrist and femur fractures and a progressive and higher increase after 50 years was observed with significantly higher values than those observed in men of the same age. Finally, first admissions to hospital for femur and wrist fractures (representing the complication of osteoporosis) in our region were 5.9% of the total admissions in the Orthopedic Departments in subjects aged over 50 years; these fractures accounted for 0.65% of the total Apulian population of the same age. This datum, although underestimated, could represent the prevalence of osteoporosis in Apulia.

Twenty-five patients with radiological and clinical evidence of osteoporosis were studied. Nineteen patients received oral phosphorus at a dose of 1,000 mg/die for 10 days followed by salmon calcitonin (100 U MRC/die) for 20 days. Six patients received only oral calcium at a dose of 1,000 mg/die). In the first group, a significant increase in serum osteocalcin and parathyroid hormone, after administration of phosphorus and persisting after treatment with salmon calcitonin, was found. No variation in the controls was observed. In a later study, a significant increase in serum 1,25 dihydroxyvitamin D (1,25(OH)2D3), after receiving phosphorus and persisting after salmon calcitonin, was demonstrated. In accordance with the authors' results, phosphorus could be considered a useful activator of bone formation and this stimulus by parathyroid hormone was mediated. Finally, the positive effects of phosphorus on circulating 1,25(OH)2D3 must be considered for a good treatment protocol of osteoporosis.

In order to examine the effects of vitamin D on osteoblast function and to evaluate if osteoporotic and normal osteoblasts show a different behaviour in response to vitamin D, this report investigates the changes in osteocalcin production, after 1,25-dihydroxy-vitamin D3 stimulation of cultured osteoblasts derived from osteoporotic patients. Our results indicate an inadequate osteoblastic function in osteoporosis and demostrate that 1,25-dihydroxy-vitamin D3 can stimulate the metabolic activity of human osteoblasts in vitro. Considering that osteoporotic bone samples were representative of senile osteoporosis, our results may indicate a different metabolic phenotype in osteoporotic osteoblasts compared with normal osteoblasts. The increased osteocalcin production after 1,25-dihydroxy-vitamin D3 stimulation of osteoporotic osteoblasts suggests a reduced, but not absent, anabolic function in senile osteoporotic osteoblasts. The results of this study confirm the validity of vitamin D3 to treat senile osteoporosis and suggest the need of higher vitamin D3 intake in senile osteoporotic patients than in younger subjects. [ABSTRACT FROM AUTHOR]

Objectives: To compare the effect of a soy rich diet and hormone replacement therapy (HRT) on the main biomarkers of bone turnover and bone mineral density (BMD) at postmenopausal age.Methods: 187 healthy asymptomatic postmenopausal women, aged 39-60, were recruited and randomized into a soy rich diet group, a HRT group, and a control group. Bone biomarkers and BMD were evaluated at baseline and after 6 months at the end of the study.Results: Diet is not as effective as HRT in reducing the postmenopausal turnover; however diet stimulates bone osteoblastic activity, as evidenced by significant increase in osteocalcin concentrations. BMD decreases significantly only in the control group, but not in the intervention groups.Conclusions: Our data suggest that soy products could be effective in reducing the risk of osteoporosis in asymptomatic postmenopausal women, but our findings should be confirmed before recommending the diet as a valid alternative to HRT. [ABSTRACT FROM AUTHOR]