A practical approach for anabolic treatment of bone fragility with romosozumab.

BACKGROUND: Romosozumab, a fully humanized anti-sclerostin-antibody, is a bone-builder stimulating osteoblasts and inhibiting osteoclast by activation of the canonical Wnt-beta catenin signaling. This unique mechanism of action has the potential to address unmet needs in osteoporosis management. METHODS: The multifaceted practical clinical issues related to romosozumab are discussed, especially focusing on the rationale of employing a sclerostin inhibitor to target bone fragility as first line or second line treatment in post-menopausal osteoporosis and in males at increased risk of fractures. RESULTS: Four randomized clinical trials with several post-hoc analyses and more than ten observational studies have consistently demonstrated that romosozumab is effective in rapidly increasing bone mineral density (BMD) and decreasing risk of vertebral, non-vertebral and hip fractures in post-menopausal women at very-high risk of fractures. In male osteoporosis, only data on BMD are available. Noteworthy, romosozumab was shown to be more effective and rapid than teriparatide in improving BMD, bone structure and strength at the hip, especially in women already treated with anti-resorptive drugs. Interestingly, even if romosozumab displays best results in treatment-naïve patients, its favourable effects on BMD were observed even in women previously treated with teriparatide or denosumab, although to a lesser extent. CONCLUSIONS: Based on the available evidence, romosozumab could be proposed as ideal drug in several clinical settings, such as non-fractured post-menopausal women at very-high risk of fractures, patients with recent hip fracture, patients non responder to bisphosphonates and short-term denosumab therapy.

Expert opinion on the management of patients with osteoporosis with anabolic drugs in Italy.

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.

Secukinumab retention rate is greater in patients with psoriatic arthritis presenting with axial involvement.

Psoriatic arthritis (PsA) is an inflammatory disease characterized by peripheral and axial involvement. Biological disease-modifying antirheumatic drugs (bDMARDs) are the mainstream treatment for PsA and bDMARDs retention rate is a proxy for the drug's overall effectiveness. However, it is unclear whether IL-17 inhibitors can have a higher retention rate than tumor necrosis factor (TNF) inhibitors, in particular in axial or peripheral PsA. A real-life observational study was conducted on bDMARD naïve PsA patients initiating TNF inhibitors or secukinumab. Time-to-switch analysis was carried out with Kaplan-Meyer curves (log-rank test) truncated at 3 years (1095 days). Sub-analyses of Kaplan-Meyer curves between patients presenting with prevalent peripheral PsA or prevalent axial PsA were also conducted. Cox regression models were employed to describe predictors of treatment switch/swap. Data on 269 patients with PsA naïve to bDMARD starting either TNF inhibitors (n=220) or secukinumab (n=48) were retrieved. The overall treatment retention at 1 and 2 years was similar for secukinumab and TNF inhibitors (log-rank test p NS). We found a trend towards significance in the Kaplan-Meyer at 3 years in favor of secukinumab (log-rank test p 0.081). Predominant axial disease was significantly associated with a higher chance of drug survival in secukinumab users (adjusted hazard ratio 0.15, 95% confidence interval = 0.04-0.54) but not in TNF inhibitor users. In this real-life, single-center, study on bDMARD naïve PsA patients, axial involvement was associated with longer survival of secukinumab but not of TNF inhibitors. Drug retention of secukinumab and TNF inhibitors were similar in predominantly peripheral PsA.

Association between exposure to fine particulate matter and osteoporosis: a population-based cohort study.

Long-term environmental air pollution exposure was associated with osteoporosis' risk in a cohort of women at high risk of fracture. Cortical sites seemed to be more susceptible to the exposure's effect. INTRODUCTION: Environmental air pollution has been associated with disruption of bone health at a molecular level. Particulate matter (PM) exposure can simultaneously stimulate bone resorption and halt bone formation. The primary aim of the present study is to describe the association between long-term exposure to PM and osteoporosis in a large cohort of women at high risk of fracture. METHODS: Clinical, demographic, and densitometric data were extracted from the DeFRAcalc79 dataset, which gathers data on women at risk for osteoporosis. Data on the monitoring of PM10 and PM2.5 concentrations were retrieved from the Italian institute of environment protection and research (Istituto Superiore per la Protezione e la Ricerca Ambientale, ISPRA). Generalized linear models with robust estimators were employed to determine the relationship between BMD and PM long-term exposure. RESULTS: A total 59,950 women from 110 Italian provinces were included in the study. PM 2.5 exposure was negatively associated with T-score levels at the femoral neck (ß -0.005, 95 CI -0.007 to -0.003) and lumbar spine (ß -0.003, 95% CI -0.006 to -0.001). Chronic exposure to PM2.5 above 25 µg/m3 was associated with a 16% higher risk of having osteoporotic T-score at any site (aOR 1.161, 95% CI 1.105 to 1.220), and exposure to PM10 above 30 µg/m3 was associated with a 15% higher risk of having osteoporotic T-score at any site (aOR 1.148, 95% CI 1.098 to 1.200). CONCLUSION: Long-term exposure to air pollution was associated with higher risk of osteoporosis. Femoral neck site seemed to be more susceptible to the detrimental effect of PM exposure than lumbar spine site. KEY MESSAGE: Exposure to air pollution is associated with osteoporosis, mainly at femoral site.

Efficacy of mud plus bath therapy as compared to bath therapy in osteoarthritis of hands and knees: a pilot single-blinded randomized controlled trial.

The primary objective of this study was to assess the efficacy of mud plus bath therapy in comparison to bath therapy alone in hand and knee osteoarthritis (HOA and KOA). We conducted a single-blinded randomized controlled trial (RCT). Patients were randomly assigned to either mud plus bath therapy (group 1) or balneotherapy (group 2). The primary outcome was a change in AUSCAN questionnaire for HOA and in WOMAC for KOA at month 12. Evaluations were performed at baseline (B), immediately after the interventions (week 2, W2) and after 3 (M3), 6 (M6), 9 (M9) and 12 (M12) months. 37 patients with KOA and 52 with HOA were randomized in the study. In HOA patients, AUSCAN pain improved more in group 1 compared to group 2 at M3, M6 and M12 (p<0.001, p=0.001 and p=0.038, respectively). AUSCAN stiffness improved more in group 1 at M3 (p=0.001). AUSCAN function improved more at M3, M6, M9 and M12 (p=0.001, p=0.001, p=0.014 and p=0.018, respectively). Regarding, KOA, WOMAC function decreased more prominently in group 1 compared to group 2 at M9 (p=0.007). The absolute values of WOMAC function at M6 and M9 were lower in group 1 compared to group 2 (p=0.029 and p=0.001, respectively). WOMAC pain absolute values were lower in group 1 at W2 (p=0.044) and at M9 (p=0.08). We conducted a RCT on the efficacy of mud plus balneotherapy over balneotherapy alone in HOA and KOA. We found that mud plus balneotherapy was more effective than balneotherapy alone on clinical outcomes of HOA. Differences in clinical outcomes of KOA were not significant, yet numerically higher.

Vitamin D and disease severity in coronavirus disease 19 (COVID-19).

The role of 25-OH-vitamin D in the assessment of coronavirus disease 19 (COVID-19) has not been investigated. We sought to investigate the prevalence of 25-OH-vitamin D deficiency among COVID-19 patients, and to determine the associations between 25-OH-vitamin D status and the severity of the disease. We have conducted a retrospective observational study of COVID-19 patients admitted to the University of Verona Hospital Trust. Demographic, clinical and biochemical parameters were collected at hospital admission, and serum 25-OH-vitamin D levels were measured. The following outcomes were assessed: arterial partial oxygen pressure (PaO2); C-reactive protein (CRP); length of hospitalization; requirement of oxygen therapy; non-invasive ventilation (NIV); mechanical ventilation; and death. Among 61 patients enrolled, 72.1% was 25-OH-vitamin D deficient (<20 ng/mL) and 57.4% had 25-OHvitamin D <15 ng/mL. Patients with arterial PaO2 <60 mmHg had significantly lower mean 25-OH-vitamin D levels compared to patients with PaO2 ≥60 mmHg (13.3 ng/mL vs 20.4 ng/mL respectively, p=0.03). Vitamin D deficiency was associated with 3-fold higher risk of having arterial pO2 <60 mmHg. 25-OH-vitamin D deficiency was associated with increased CRP and dyspnea. 25-OH-vitamin D deficiency was associated with more severe systemic inflammatory response and respiratory failure in COVID-19 patients.

Risk of fragility fractures in obesity and diabetes: a retrospective analysis on a nation-wide cohort.

This study aims to investigate the role of obesity and diabetes on bone health in a nation-wide cohort of women with high risk of fracture. INTRODUCTION: The role of obesity and diabetes on fracture risk is yet poorly understood. Body mass index (BMI) and bone mineral density (BMD) are strongly correlated; however, patients with elevated BMI are not protected against fractures, configuring the obesity paradox. A similar controversial association has been also found in diabetic patients. Herein, we present a retrospective analysis on 59,950 women. METHODS: Using a new web-based fracture risk-assessment tool, we have collected demographic (including BMI), densitometric, and clinical data (including history of vertebral or hip and non-vertebral, non-hip fractures, presence of comorbidities). We performed a propensity score generation with 1:1 matching for patients in the obese (BMI ≥ 30) and non-obese (BMI < 30) groups, in the diabetics and non-diabetics. Propensity score estimates were estimated using a logistic regression model derived from the clinical variables: age, lumbar spine T-score, and femoral neck T-score. RESULTS: We found an association between diabetes and fractures of any kind (OR 1.3, 95% CI 1.1-1.4 and 1.3, 95% CI 1.2-1.5 for vertebral or hip fractures and non-vertebral, non-hip fractures, respectively). Obesity, on the other hand, was significantly associated only with non-vertebral, non-hip fractures (OR 1.3, 95% CI 1.1-1.6). To estimate the individual effect of obesity and diabetes on bone health, we ran sensitivity analyses which included obese non-diabetic patients and non-obese diabetic patients, respectively. CONCLUSIONS: Non-obese diabetics had the highest risk of vertebral or hip fracture, whereas obese non-diabetics predominantly had non-vertebral, non-hip fracture's risk. These results should raise awareness in clinical practice when evaluating diabetic and/or obese patients.

Concentric left ventricular remodelling is associated with subclinical systolic dysfunction in patients with psoriatic arthritis.

Objectives: Subclinical left ventricular (LV) abnormalities have been reported in echocardiographic studies of patients with psoriatic arthritis (PsA). Left ventricular systolic dysfunction (LVSD) often coexists with concentric LV remodelling, an unfavourable prognostic factor that is commonly found in patients at high cardiovascular risk. However, it is unclear whether PsA is associated with concentric LV remodelling. This cross-sectional study assesses the prevalence of and factors associated with concentric LV remodelling in a cohort of patients with PsA, and tests the hypothesis that concentric LV remodelling is a major determinant of LVSD in PsA. Method: We evaluated 101 adults attending an outpatient clinic with PsA diagnosed according to the ClASsification criteria for Psoriatic ARthritis (CASPAR). All patients were free of cardiovascular disease. Patients with PsA were compared with 101 controls matched for age, gender, body mass index, hypertension, and diabetes. Echocardiography was performed: concentric LV remodelling was defined if the relative wall thickness was > 0.43; stress-corrected mid-wall shortening was used as an index of LVSD and considered impaired if < 86.5%. Results: Concentric LV remodelling was found in 58% of patients with PsA and 18% of controls (p < 0.001). LVSD was found in a significantly higher proportion of patients with PsA (56%, p < 0.001) than controls. The presence of PsA yielded a 10-fold higher probability of having LVSD [odds ratio (OR) 9.6, 95% confidence interval (CI) 4.2-21.9, p < 0.0001]. In patients with PsA, concentric LV remodelling increased the risk of LVSD four-fold (OR 3.7, 95% CI 1.3-10.2, p = 0.013). Conclusion: Most asymptomatic patients with PsA have concentric LV remodelling, which is closely associated with subclinical LVSD.

Vitamin D supplementation: much ado about nothing.

The scientific interest and the number of papers dealing with vitamin D supplementation has greatly grown in the last decades. Unfortunately, expert consensus on many clinical aspects of this topic is still lacking. In addition, data coming from recent clinical trials and meta-analyses seem to strongly put into doubt the real benefit of vitamin D supplementation, on both skeletal and extra-skeletal outcomes. This is further confusing since they seem to completely contradict the considerable body of evidence provided from previous epidemiological studies. This paper aims to analyze these new data in order to shed light onto the debated issues.

Correction to: Bone metabolism in patients with anorexia nervosa and amenorrhoea.

Unfortunately, the sixth author name was incorrectly spelled as "S. Fassio" instead of "A. Fassio" in the original publication.

Different fracture risk profile in patients treated with anti-osteoporotic drugs in real-life.

In this retrospective study, we intended to investigate the baseline fracture risk profile in patients who started treatment with different anti-osteoporotic medications. We analyzed retrospectively the fracture risk calculated with DeFRA, a validated FRAX derived tool, in women who started an anti-osteoporotic treatment from 2010 to 2017. We analyzed baseline data of 12,024 post-menopausal women aged over 50 years. Teriparatide initiators had a baseline 10-year risk of major osteoporotic fracture of 82.1% with a Standard Deviation (SD) of 66.5%. Denosumab initiators and zoledronic acid initiators had a greater 10-year baseline risk of fracture (54.3%, SD 46.5% and 47.0%, SD 42.0 respectively) than patients initiated on alendronate (24.9%, SD 34.6%) and patients initiated on risedronate (23.9%, SD 24.1%). Using DeFRA, a FRAX™ derived tool, we showed significantly different fracture risk profiles in women who were started on various therapeutic agents for the treatment of osteoporosis in routine clinical practice.

Radiofrequency echographic multispectrometry compared with dual X-ray absorptiometry for osteoporosis diagnosis on lumbar spine and femoral neck.

An innovative, non-ionizing technique to diagnose osteoporosis on lumbar spine and femoral neck was evaluated through a multicenter study involving 1914 women. The proposed method showed significant agreement with reference gold standard method and, therefore, a potential for early osteoporosis diagnoses and possibly improved patient management. INTRODUCTION: To assess precision (i.e., short term intra-operator precision) and diagnostic accuracy of an innovative non-ionizing technique, REMS (Radiofrequency Echographic Multi Spectrometry), in comparison with the clinical gold standard reference DXA (dual X-ray absorptiometry), through an observational multicenter clinical study. METHODS: In a multicenter cross-sectional observational study, a total of 1914 postmenopausal women (51-70 years) underwent spinal (n = 1553) and/or femoral (n = 1637) DXA, according to their medical prescription, and echographic scan of the same anatomical sites performed with the REMS approach. All the medical reports (DXA and REMS) were carefully checked to identify possible errors that could have caused inaccurate measurements: erroneous REMS reports were excluded, whereas erroneous DXA reports were re-analyzed where possible and otherwise excluded before assessing REMS accuracy. REMS precision was independently assessed. RESULTS: In the spinal group, quality assessment on medical reports produced the exclusion of 280 patients because of REMS errors and 78 patients because of DXA errors, whereas 296 DXA reports were re-analyzed and corrected. Analogously, in the femoral group there were 205 exclusions for REMS errors, 59 exclusions for DXA errors, and 217 re-analyzed DXA reports. In the resulting dataset (n = 1195 for spine, n = 1373 for femur) REMS outcome showed a good agreement with DXA: the average difference in bone mineral density (BMD, bias ± 2SD) was -0.004 ± 0.088 g/cm2 for spine and - 0.006 ± 0.076 g/cm2 for femur. Linear regression showed also that the two methods were well correlated: standard error of the estimate (SEE) was 5.3% for spine and 5.8% for femur. REMS precision, expressed as RMS-CV, was 0.38% for spine and 0.32% for femur. CONCLUSIONS: The REMS approach can be used for non-ionizing osteoporosis diagnosis directly on lumbar spine and femoral neck with a good level of accuracy and precision. However, a more rigorous operator training is needed to limit the erroneous acquisitions and to ensure the full clinical practicability.

Radiological features of knee joint synovial chondromatosis.

Synovial chondromatosis (SC) is a rare condition with a very variable clinical presentation, thus making the diagnosis not immediate. We report a case of massive primary SC of the knee, properly evaluated with X-rays, ultrasonography and magnetic resonance imaging and successfully treated with an arthroscopic approach.

Bone metabolism in patients with anorexia nervosa and amenorrhoea.

PURPOSE: Aim of this study is focusing on bone metabolism in AN patients with amenorrhoea and related estrogen deficiency effects. METHODS: AN patients were compared both with healthy females and with postmenopausal women (reference model for estrogen deficiency). The study sample included 81 females with AN. Laboratory tests [25-OH vitamin D, bone turnover markers, intact parathyroid hormone, sclerostin (SOST) and dickkopf-related protein (DKK1)] and dual energy X-ray absorptiometry (DXA) were taken into account. RESULTS: AN patients had higher levels of C-terminal telopeptide of type I collagen (CTX) than both control groups. AN adolescents had CTX higher than AN young adults. In postmenopausal women, intact N-propeptide of type I collagen was higher if compared with each other group. In AN groups, Dickkopf-related protein 1 was significantly lower than the two control groups. No differences were found in sclerostin except in adolescents. In AN adolescents, DXA values at femoral sites were higher than in AN young adults and a positive correlation was found with body weight (p < 0.01) and with fat mass evaluated using DXA (p < 0.01). CONCLUSIONS: AN women with amenorrhoea have an increased bone resorption like postmenopausal women but bone formation is depressed. The consequent remodeling uncoupling is considerably more severe than that occurring after menopause.

Long-term Effects of Neridronate in Adults with Osteogenesis Imperfecta: An Observational Three-Year Italian Study.

The aim of this study was to assess the long-term efficacy and safety of i.v. neridronate in the treatment of osteogenesis imperfecta (OI). One hundred and fourteen patients affected by OI were included in the study. Neridronate was administered by i.v. infusion at the dosage of 2 mg/kg, up to a maximum of 100 mg at three-month intervals for 3 years. Dual X-ray absorptiometry of the lumbar spine, hip, and ultradistal and proximal radius were evaluated every 6 months. Blood calcium, phosphate, albumin, fasting urinary calcium/creatinine ratio, total serum alkaline phosphatase, and bone alkaline phosphatase were obtained at baseline and every 3 months. The mean lumbar spine and total hip BMD significantly increased from baseline to any time point (p < 0.001). The mean ultradistal radius BMD significantly increased from baseline only at month 18 (p = 0.026), 30 (p = 0.046), and 36 (p = 0.013), respectively. The mean proximal radius BMD did not change during the whole observation. The levels of bone turnover markers significantly decreased from baseline to any post-baseline observation time. The study was not able to find any statistically significant effect on fracture risk (p = 0.185). The percentage of patients with fractures was unaltered during treatment as compared to the 3-year period before treatment. The most common AEs were fragility fractures, back pain, arthralgia, fever, and joint sprain. An acute phase reaction was reported in 26 (22.8%) patients. None of the reported SAEs were considered as treatment-related. Long-term treatment with i.v. neridronate has positive effects on BMD and bone turnover markers with a good safety profile, although no significant effect on the risk of fracture was observed.

Longitudinal Evaluation of Bone Mineral Density and Bone Metabolism Markers in Patients with Indolent Systemic Mastocytosis Without Osteoporosis.

Systemic Mastocytosis has been long identified as a potential cause of osteoporosis; nevertheless, data regarding longitudinal variation of bone mineral density (BMD) in patients with indolent systemic mastocytosis (ISM) are missing . We studied BMD variation at lumbar spine and proximal hip after 30-month (±6 months) follow-up in a large cohort of patients (83) with ISM without osteoporosis, supplementated with vitamin D and/or calcium when needed. We also analyzed the correlation between variation of BMD, basal serum tryptase levels and bone turnover markers (BTM). Sixty-four percent of our population was male; mean age was 52.1 (±11.5) years. Vitamin D insufficiency (serum levels of 25-OH-vitamin D, 25OHD, lower than 75 nmol/L) was found in more than 70 % of patients. After a follow-up of 30 ± 6 months with only vitamin D (5000-7500 IU weekly of oral cholecalciferol) or calcium (500 mg/die) supplementation when needed, we observed 2.1 % increase in BMD at lumbar spine, with no significant changes at hip. At the end of follow-up, almost 60 % of patients showed 25OHD serum levels still lower than recommended, despite vitamin D supplementation. Reduction in BMD after follow-up significantly correlated with high C-telopeptide of type I collagen serum levels at the time of diagnosis. In patients with ISM without osteoporosis, a routinary BMD evaluation within a time <2 years is not justified, except in the presence of elevated BTM. In these patients, vitamin D supplementation is frequently needed.

Drug-induced osteonecrosis of the jaw: the state of the art.

Osteonecrosis of the jaw (ONJ) is a rare adverse event of antiresorptive drugs such as bisphosphonates (BP) and denosumab (DMAb). The diagnosis of ONJ is considered in cases where exposed bone in the maxillofacial region does not heal within 8 weeks in a patient previously treated with an antiresorptive agent. In patients with osteoporosis, ONJ is reported as a very rare adverse event while in oncologic patients with bone metastases or malignant hypercalcemia the incidence is significantly higher (up to the 1-10% of the patients). The pathophysiology of ONJ is still not completely understood but it is multi-factorial. ONJ is a condition associated with poor oral health, oral surgery, and use of antiresorptive agents. Prevention is of paramount importance especially in cancer patients, in whom the large majority of cases of ONJ (>90%) are reported, but it should also be considered in osteoporotic patients, especially during dental surgical procedure. Some simple prevention procedures are effective in reducing the risk of its appearance. When ONJ unfortunately occurs, the large majority of patients can be managed conservatively. In conclusion, ONJ is a rare condition associated with antiresorptive drugs. Both osteoporotic and oncologic patients should be well informed about its low absolute risk and regarding the fact that the benefits of antiresorptive therapy far outweigh this potential risk of ONJ.

Effects of secukinumab on serum adipocytokines: preliminary data.

Psoriatic arthritis (PsA) is a chronic inflammatory disease that affects joints, connective tissues and the axial skeleton. Metabolic syndrome is an independent risk factor for psoriasis (Pso) development and is associated with more severe forms of Pso. Adipocytokines are secreted by white adipose tissue and are thought to link obesity with the development of metabolic and cardiovascular diseases. Secukinumab is a new monoclonal antibody with a different mechanism of action. This antibody selectively binds to and neutralizes interleukin-17 (IL-17) and it has shown efficacy in the treatment of PsA. The aim of this study was to evaluate the possible interferences of secukinumab on different adipocytokines. We enrolled 28 patients with PsA, classified with the CASPAR criteria. Serum samples were stored at baseline and then at the first, the third and the sixth month of therapy. Resistin, chemerin, adiponectin and C-reactive protein (CRP) were dosed. When tested globally, none of the adipokine tested showed any statistically significant variation. However, when the male group was tested, both resistin and chemerin at M6 showed a significant decrease from baseline. CRP did not show any variation at any time point. Our study demonstrated that treatment with secukinumab has little influence on the levels of adipokines tested within the first six months of treatment even though it might exert different influence between males and females from a metabolic perspective. Further studies with greater numbers of patients are needed to determine whether these preliminary results have clinical relevance.

Prevalence and incidence of osteoporotic fractures in patients on long-term glucocorticoid treatment for rheumatic diseases: the Glucocorticoid Induced OsTeoporosis TOol (GIOTTO) study.

Osteoporosis and fractures are common and invalidating consequences of chronic glucorticoid (GC) treatment. Reliable information regarding the epidemiology of GC induced osteoporosis (GIOP) comes exclusively from the placebo group of randomized clinical trials while observational studies are generally lacking data on the real prevalence of vertebral fractures, GC dosage and primary diagnosis. The objective of this study was to evaluate the prevalence and incidence of osteoporotic fractures and to identify their major determinants (primary disease, GC dosage, bone mineral density, risk factors, specific treatment for GIOP) in a large cohort of consecutive patients aged >21 years, on chronic treatment with GC (≥5 mg prednisone - PN - equivalent) and attending rheumatology centers located all over Italy. Glucocorticoid Induced OsTeoporosis TOol (GIOTTO) is a national multicenter cross-sectional and longitudinal observational study. 553 patients suffering from Rheumatoid Arthritis (RA), Polymyalgia Rheumatica (PMR) and Connective Tissue Diseases (CTDs) and in chronic treatment with GCs were enrolled. Osteoporotic BMD values (T score <-2.5) were observed in 28%, 38% and 35% of patients with CTDs, PMR or RA at the lumbar spine, and in 18%, 29% and 26% at the femoral neck, respectively. Before GC treatment, prevalent clinical fractures were reported by 12%, 37% and 17% of patients with CTDs, PMR, or RA, respectively. New clinical fragility fractures during GC treatment were reported by 12%, 10% and 23% of CTDs, PMR and RA patients, respectively. Vertebral fractures were the prevailing type of fragility fracture. More than 30% of patients had recurrence of fracture. An average of 80% of patients were in supplementation with calcium and/or vitamin D during treatment with GCs. Respectively, 64%, 80%, and 72% of the CTDs, PMR and RA patients were on pharmacological treatment for GIOP, almost exclusively with bisphosphonates. The GIOTTO study might provide relevant contributions to clinical practice, in particular by highlighting and quantifying in real life the prevalence of GIOP and relative fractures, the frequency of the main risk factors, and the currently sub-optimal prevention. Moreover, these results emphasize the importance of the underlying rheumatic disease on the risk of GIOP associated fractures.

Teriparatide and denosumab combination therapy and skeletal metabolism.

Several therapies are available for osteoporis. Understanding the bone turnover changes and their mutual realtionship gives an overall view and might lead to a target therapy INTRODUCTION: The aim of this study is to compare the changes in bone turnover markers in patients treated with either denosumab alone, teriparatide (TPTD) alone, or in a third therapeutic scheme, when TPTD was added to patients previously treated with denosumab. METHODS: Fifty-nine women over 65 years old with severe postmenopausal osteoporosis (evidence of at least two moderate-severe vertebral fractures) were enrolled in the study. Serum samples were collected every 3 months. They were assayed for intact N-propeptide of type I collagen (P1NP), C-terminal telopeptide of type I collagen (CTX), intact parathyroid hormone (PTH), 25 hydroxy-vitamin D (25 OHD), Sclerostin (SOST), and Dickkopf-related protein 1 (DKK1). Bone mass density was assessed by dual-energy X-ray absorptiometry at the lumbar spine and at the total hip. RESULTS: In the groups treated only with TPTD or with denosumab, bone turnover markers increased and decreased, respectively. In TPTD group, a later significant increase in DKK1 was observed, while in denosumab group, a progressive increase in SOST was associated with a progressive significant decrease in DKK1. In the group treated first with denosumab and in which TPTD was added 3 months later, both CTX and P1NP increased 3 months after the beginning of TPTD. The strong effect of denosumab on bone turnover seems to be reversed by TPTD treatment. CONCLUSIONS: In this study, we showed that TPTD is able to express its biological activity even when bone turnover is fully suppressed by denosumab treatment. The combination therapy is associated with significant increases in both DKK1 and SOST.