Inhibition of the RANKL with denosumab has no effect on circulating markers of atherosclerosis in women with postmenopausal osteoporosis: a pilot study.

PURPOSE: We evaluated the early effect of denosumab on circulating markers of atherosclerosis in women with postmenopausal osteoporosis. METHODS: Denosumab (60 mg) was administered subcutaneously every 6 months (m) in 27 women (mean age 75 ± 5 years) with postmenopausal osteoporosis and high cardiovascular risk for a total of 24 m. Zoledronic acid was administered in 6 age-matched women as a single intravenous dose. Serum levels of vascular cell adhesion protein 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), E and P selectin, CD-40 ligand (CD40L), interleukin-6 (IL-6), matrix metalloproteinase (MMP) 1 and 9, monocyte chemoattractant protein-1 (MCP-1), fibrinogen (FBG), and high sensitivity C-reactive protein (hs-CRP) were measured at baseline, 15 days (d), 2, 6 and 12 m after dosing. In the denosumab group, observation was extended to 24 m as secondary endpoint. RESULTS: Serum ICAM-1 levels showed significant increase in the zoledronic acid group (+18 ± 0.1%; p < 0.01) at 12 m. In the denosumab group, we observed a significant increase in serum CD40L (+2 ± 0.8%; p < 0.001), MMP-1 (+11 ± 0.4%, p < 0.02), and MMP-9 (+39.4 ± 0.8%, p < 0.01) at 24 m. There was a significant increase in serum FBG and hs-CRP in both groups at 12 m (denosumab:+2.2 ± 0.2% and +50.3 ± 1.6%; zoledronic acid: +9.4 ± 0.1 and +81.8 ± 0.8%; p < 0.01). No significant between-group differences were found. CONCLUSIONS: 24-m treatment with denosumab has no effect on the circulating markers of atherosclerosis in women with postmenopausal osteoporosis. Fluctuation of serum ICAM-1, CD40L, MMPs, FBG and hs-CRP can be ascribed to perturbation of immunological mechanisms stimulated by denosumab and zoledronic acid.

Prevalence of kidney stones and vertebral fractures in primary hyperparathyroidism using imaging technology.

CONTEXT: The fourth International Workshop on the Management of Asymptomatic Primary Hyperparathyroidism (PHPT) has recently suggested that skeletal and renal imaging be routinely conducted. So far, no study has systematically assessed this issue. OBJECTIVE: The objective was to evaluate the prevalence of kidney stones (KS) and vertebral fractures (VFs) in a cohort of patients with PHPT utilizing noninvasive imaging technology. DESIGN: This was a prospective study evaluating patients consecutively diagnosed with PHPT in a single center over a 5-year period (2009-2013). SETTING: The setting was a referral center. PATIENTS: There were a total of 140 patients with PHPT (127 women [18 premenopausal and 109 postmenopausal] and 13 men; mean age, 63.2 ± 11 y). MAIN OUTCOMES MEASURES: Main outcome measures were the prevalence of KS by abdominal ultrasound, osteoporosis by dual-energy x-ray absorptiometry (DXA) (lumbar spine, femoral neck, total hip, and distal 1/3 radius), and VFs by vertebral spine x-ray, with attention to those categorized as symptomatic or asymptomatic. RESULTS: Fifty-five percent of all subjects had KS by ultrasound, 62.9% had osteoporosis by T-score at any site, and 35.1% had VFs by x-ray. There was no difference in the incidence of VFs and densitometric osteoporosis between symptomatic and asymptomatic patients (VFs, 34.4 vs 34.7%; osteoporosis by DXA, 59.4 vs 65.8%), whereas more KS were detected in symptomatic (78%) than asymptomatic (35.5%). Twenty-two percent of patients classified as asymptomatic at baseline without osteoporosis by DXA were found to have KS and/or VFs. CONCLUSIONS: Nephrolithiasis and VFs are common in asymptomatic subjects with PHPT. The results provide evidence in support of recent recommendations that a more proactive approach be taken to detect silent bone and stone disease in asymptomatic PHPT.

Update on vitamin D: pros and cons.

Controversies on vitamin D currently represent a challenging topic in mineral metabolism research. In particular, current guidelines on vitamin D supplementation did not report consistent recommendation and the issue related to beneficial vs harmful effects of loading vitamin D doses did not lead to any firm universal conclusion. Finally, serum and clinical outcomes of vitamin D supplementation, particularly as far as extra-skeletal effect of the hormone, need to be further investigated.

Acute effect of zoledronic acid on the risk of cardiac dysrhythmias.

There have been recent concerns regarding the risk of serious adverse events, such as cardiac dysrhythmia and atrial fibrillation (AF), associated with bisphosphonate use in osteoporosis. This open-label, non-randomized, crossover pilot study evaluated short-term effects of zoledronic acid and placebo on the occurrence of cardiac dysrhythmias and prodysrhythmic profile in postmenopausal women with osteoporosis and low risk of cardiac dysrhythmias. Fifteen postmenopausal women (mean age 70.7 ± 6.9 years) with osteoporosis received placebo infusion on day 1 and zoledronic acid 5 mg on day 7. Standard 12-lead resting EKG measured QT parameters at baseline and up to 24 h after infusion. Continuous 24-h EKG assessed dysrhythmic events and heart rate variability (HRV) for 24 h after infusion. There were no statistically significant differences in resting EKG parameters between placebo and zoledronic acid: QTc (404.28 ± 9.28 and 410.63 ± 18.43 ms), no significant differences in mean serum electrolytes at baseline and after infusion, and no significant association between QT/QTc parameters and serum electrolytes before and after each infusion (QTc: 401.83 ± 17.73 for zoledronic acid and 404.65 ± 16.79 for placebo). There was no significant difference in HRV parameters between placebo and zoledronic acid, and no dysrhythmias were recorded at rest or with 24 h EKG monitoring. Zoledronic acid does not produce dysrhythmia or prodysrhythmic effects in the short term. Among possible mechanisms proposed for cardiac dysrhythmias with zoledronic acid, no serum electrolyte or autonomous nervous system balance perturbations have been reported.

Vitamin d and its relationship with obesity and muscle.

The skin synthesis of vitamin D represents the first step of a metabolic pathway whose features have been extensively studied and clarified in the last decades. In particular, the production of active and inactive forms of the hormone and the actions of the corresponding enzymes have offered new insights into the knowledge of vitamin D metabolism. Additionally, the description of the different organs and tissues expressing the vitamin D receptor and its possible functions, as well as its genetic determinants, have allowed focusing on the interrelationship between vitamin D and many physiological and pathological functions. In this context, many studies reported the association between vitamin D and adipose tissue metabolism, as well as the possible role of the hormone in obesity, weight, and fat mass distribution. Finally, many reports focused on the vitamin D-related effects on skeletal muscle, particularly on the mechanisms by which vitamin D could directly affect muscle mass and strength. This paper is mainly aimed to review vitamin D metabolism and its relationship with obesity and skeletal muscle function.

Hospital care for primary hyperparathyroidism in Italy: a 6-year register-based study.

OBJECTIVE: Primary hyperparathyroidism (PHPT) is one of the most frequently diagnosed endocrine disorders, but few studies have focused on hospital management of the disease in Europe. We investigated the frequency of hospital admission for diagnosis and surgical treatment of PHPT in Italy. DESIGN: A retrospective study was conducted for investigating the hospital care for PHPT in Italy. METHODS: We retrieved data from the 'Record of Hospital Discharge' of the Italian Health Ministry, from 2006 to 2011, and analyzed the codes corresponding to PHPT-related diagnoses and surgical procedures. RESULTS: Overall, 46 275 hospitalization episodes for PHPT were identified during the entire period (69% in women and 31% in men; mean age 63.3±39.8 years). Patients' mean age significantly increased during the years (P<0.001). The mean length of stay was 8.2±10.5 days (28% of the episodes requiring <3 days of stay). Admissions for surgical procedures were 12 457 accounting for 26.9% of the total hospitalizations. There was a trend to a significant increase in the percentage of surgery (P<0.05). The mean hospitalization rate for PHPT was 12.9/100 000 inhabitants per year and the trend showed a significant decrease during the period of 2006-2011 (P<0.0001). The mean hospitalization rate for PHPT surgery was 3.65/100 000 per year, which significantly increased over time (P<0.001). CONCLUSIONS: PHPT considerably influences the Italian Hospital healthcare system. We observed a tendency to a decrease in the frequency of hospitalization during the period of 2006-2011, most probably because of economic issues, a concomitant increased age of patients, and, interestingly, also a progressive increase in the percentage of surgical treatment among patients admitted for PHPT.

Quality of life in patients with primary hyperparathyroidism.

The clinical picture of primary hyperparathyroidism (PHPT) has changed over the last three decades and many asymptomatic patients are now diagnosed through the unexpected finding of high serum calcium levels. However, though not yet considered as typical features of the disease and therefore not included in the guidelines for surgery, many data are available on neuropsycological manifestations and their impact on quality of life in asymptomatic patients. PHPT patients indeed show early experience nonspecific symptoms, such as weakness, depression, sleep disturbance, memory loss and anxiety. Although the underlining mechanisms have not been still identified, the prevalence of psychiatric and cognitive deficits has been investigated in many studies, as well as the possible association with quality of life and well-being improvement after surgery. This article aims to review the current knowledge on quality of life in PHPT patients before and after surgery and the possible clinical implications of these findings.

Six-year follow-up of a characteristic osteolytic lesion in a patient with tumor-induced osteomalacia.

OBJECTIVE: Tumor-induced osteomalacia is a rare paraneoplastic syndrome characterized by hypophosphatemia and inappropriately normal or low 1,25-dihydroxyvitamin D. CLINICAL CASE: Here, we report a 6-year postoperative follow-up of a patient with oncogenic osteomalacia with a distinctive skeletal manifestation. The latter was characterized by an almost linear lytic lesion of a few millimeters with irregular borders, mainly involving the trabecular compartment but extending into cortical shell, located in the middle third of the right fibula. Six years after tumor resection, a sclerotic repair with a complete recovery was observed. Furthermore, we monitored a striking increase in bone mineral density throughout the observation period, reaching a peak of 73% over basal values at lumbar spine after 2 years; at total femur and radius, the peak was 47.5 and 4.6% respectively, after 4 years from tumor resection. CONCLUSIONS: We report for the first time that an osteolytic lesion may be part of the skeletal involvement in tumor-induced osteomalacia.

Management of endocrine disease: value and limitations of assessing vitamin D nutritional status and advised levels of vitamin D supplementation.

The growing attention to the role of vitamin D in skeletal and extra-skeletal diseases over the last decade induced an increased demand for vitamin D determination as well as a dramatic rise of sales of vitamin D supplement. However, several critical points in this field remain to be clarified. We lack a clear consensus about the definition of vitamin D deficiency, insufficiency, and sufficiency. The identification of different thresholds defining vitamin D status has relevant implications in clinical practice. In fact, the worldwide prevalence of low vitamin D status is highly varying according to the level of 25(OH)D utilized to define sufficiency. Therefore, the assessment of 25-hydroxyvitamin D levels may have a critical role, but a number of different technical problems associated with its determination may interfere in interpreting the results. The hydrophobic nature of vitamin D and the tight binding to its carrier (vitamin D binding protein), the different forms circulating in blood, and the issue of standardization are among the most important factors influencing the measurement of this metabolite. Another controversial point relies on the conflicting guidance on prevention and treatment of vitamin D deficiency endorsed by different medical and scientific communities. In particular, uncertainty exists about how to replete vitamin D stores, how to maintain normal 25(OH)D levels after repletion, which form of vitamin D is preferable for supplementation, and which route of administration and dosing regimens are advisable. Finally, concerns have been raised regarding vitamin D toxicity and its adverse effects.

Long-term bioavailability after a single oral or intramuscular administration of 600,000 IU of ergocalciferol or cholecalciferol: implications for treatment and prophylaxis.

CONTEXT: We previously showed that a single high dose of oral (po) cholecalciferol (D3) sharply increases serum 25-hydroxyvitamin D [25(OH)D]. OBJECTIVE: We evaluated the long-term bioavailability and metabolism of a single po or intramuscular (im) high dose of ergocalciferol (D2) or D3. DESIGN: This was a prospective intervention study. SETTING: The study was conducted in an ambulatory care setting. PATIENTS: Participants were 24 subjects with hypovitaminosis D. INTERVENTIONS: A single dose of 600,000 IU of po or im D2 or D3 was administered. MAIN OUTCOME MEASURES: Serum 25(OH)D and 1,25-dihydroxyvitamin D [1,25(OH)2D] were measured at baseline and at days 30, 60, 90, and 120 by RIA. Serum 1,25(OH)2D2, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], 24,25-hydroxyvitamin D2 [24,25(OH)D2], and 24,25-hydroxyvitamin D3 [24,25(OH)D3] were measured by liquid chromatography-tandem mass spectrometry in a subgroup of patients receiving the po formulations. RESULTS: The areas under the curve of 25(OH)D after D3 were significantly higher than those after D2 (P < .0001). Serum 25(OH)D basal difference significantly increased at day 30 with po D2 and D3 (P < .01 and P < .0001) and up to day 90 with po D3 (P < .01). The im formulations produced a slow increased, and values peaked at day 120 relative to the other time points (P < .0001). We found a decrease in 1,25(OH)2D at day 30 (P < .05) and up to day 120 (P < .001) and an increase in 1,25(OH)2D2 at day 30 (P < .01) and up to day 120 (P < .01) after po D2. Oral D2 and D3 produced increases in 24,25(OH)D2 and 24,25(OH)D3, respectively, at day 30 (P < .001). CONCLUSIONS: A po dose of 600,000 IU of D2 or D3 is initially more effective in increasing serum 25(OH)D than the equivalent im dose and is rapidly metabolized. Our RIA assay for 1,25(OH)2D may not recognize 1,25(OH)2D2.

Parathyroidectomy eliminates arrhythmic risk in primary hyperparathyroidism, as evaluated by exercise test.

OBJECTIVE: To investigate whether parathyroidectomy (PTx) reverses risk factors for arrhythmias related to the QT dynamic changes evaluated during bicycle ergometry exercise test (ET). METHODS: Twenty-four postmenopausal women with primary hyperparathyroidism (PHPT) (mean age 60.08.4 years) and 30 sex- and age-matched controls underwent ET, echocardiography, and biochemical evaluation. The following stages were considered during ET: rest, peak exercise, and recovery. The patients were randomized to two groups: 12 underwent PTx (group A) and 12 were followed-up conservatively (group B). After 6 months, the patients were studied again. RESULTS: Groups A and B showed no differences in mean baseline biochemical values, echocardiographic parameters, and QTC interval. PHPT patients showed an increased occurrence of ventricular premature beats (VPBS) during ET compared with controls (37.0 vs 6.6%, P=0.03). Serum calcium level was a predictor of VPBS (P=0.05). Mean value of QTC was in the normal range at baseline (Group A: 401±16.9; group B: 402.25±13.5 ms) but significantly lower than controls (417.8±25.1 ms, P<0.01). A negative correlation was found between QTc and calcium values (P=0.03). Physiological reduction of QTc interval from rest to peak exercise was not observed in PHPT patients before surgery. After PTx, group A had a significant reduction in VPBs compared with baseline (at baseline, 5 of 12 vs none of 12 patients after PTx, P=0.03) and a restored normal QT adaptation during ET. Group B showed no significant changes after a 6-month period. CONCLUSIONS: PTx reduces the occurrence of VPBs and restored the QTc adaptation during ET.

The effect of parathyroidectomy on chronic constipation in patients affected by primary hyperparathyroidism.

Primary hyperparathyroidism (PHPT) is usually associated with chronic constipation; however, its prevalence is not defined by standardized criteria. The aim of the study was to evaluate both the prevalence of chronic constipation, defined by the standardized Rome diagnostic criteria III (Rome III) in PHPT, and the effect of parathyroidectomy (PTx). Fifty postmenopausal PHPT patients and 50 sex- and age-matched controls were studied. Each patient underwent mineral metabolism biochemical evaluation and completed a questionnaire and a 2-week diary card about bowel habits. PHPT patients were reevaluated after 6 months. According to Rome III, 40 % of PHPT patients had chronic constipation compared with 12 % of controls (p = 0.0002). The only difference between constipated PHPT patients (group A, n = 20) and those without constipation (group B, n = 30) was higher mean PTH values (79.9 ± 18.7 ng/l vs. 65.4 ± 26.0 ng/l; p = 0.03), which predicted the presence of constipation (p = 0.004, OR 1.059, CI 1.011-1.059). Forty percent of PHPT patients had undergone PTx. In group A, constipation was resolved in 80 % of patients after PTx compared to none of the same group who had not undergone PTx (p = 0.0007). In group B, 17.6 % of patients who had not undergone PTx became, after 6 months, constipated. According to Rome III, a higher prevalence of chronic constipation in PHPT patients was observed compared with controls. PTH levels predicted constipation. A significant reduction of chronic constipation was reported following successful surgery.

Arrhythmias in primary hyperparathyroidism evaluated by exercise test.

BACKGROUND: Hypercalcemia induces arrhythmias and shortening of QT. The aim of this study was to investigate risk factors for occurrence of arrhythmias in patients with primary hyperparathyroidism (PHPT) during bicycle ergometer exercise test (ET). METHODS: Thirty PHPT postmenopausal women (mean age, 60·9 ± 8·0 years) and 30, sex and age-matched, controls underwent ET, echocardiogram and mineral metabolism biochemical evaluation. The following stages were considered during ET: rest, peak exercise, recovery (early recovery, 2 and 10 min after peak exercise). QT was corrected with Bazett's formula (QTc). RESULTS: Compared with controls, PHPT patients showed an increased occurrence of ventricular premature beats (VPBs) during ET (26·6% vs. 6·6%, P = 0·03). Being affected by PHPT predicted the onset of VPBs at peak exercise (P = 0·04) and recovery (P = 0·03), as shown by logistic regression analysis. In PHPT patients, serum calcium level was a predictor of VPBs at peak exercise (P = 0·05). QTc in patients with PHPT was in the normal range. Serum calcium level showed a negative correlation with QTc (P = 0·01) in whole sample. Compared with controls, PHTP patients had QTc significantly shorter for every stage of ET, except at peak exercise. Physiological reduction of QTc interval from rest to peak exercise was not seen in patients with PHPT, QTc at rest being the only predictor of QTc in every stage, as shown by multivariate regression analysis. CONCLUSIONS: In patients with PHPT, an increased occurrence of VPBs and a different QTc adaptation during ET were observed and may represent risk factors for major arrhythmias.

"Trabecular Bone Score" (TBS): an indirect measure of bone micro-architecture in postmenopausal patients with primary hyperparathyroidism.

BACKGROUND: Patients with primary hyperparathyroidism (PHPT) generally show reduced bone mineral density (BMD) at cortical sites with relatively preserved trabecular bone. However, the increased fracture risk at all skeletal sites suggests that areal BMD probably is not effective in capturing all the determinants of bone strength. "Trabecular Bone Score" (TBS) has been recently proposed as an indirect measure of bone micro-architecture. Our study was aimed to investigate TBS in patients with PHPT. METHODS: Seventy-three Caucasian postmenopausal women with PHPT and 74 age-matched healthy women (C) were studied. In all participants BMD at lumbar spine (LS) and at femoral sites (Neck-FN and total hip-TH) was measured by DXA and, in 67 patients and 34 C, also at the distal 1/3 of the radius (R). TBS was measured in the region of LS-BMD. Spine X ray was assessed in all patients. RESULTS: Mean TBS values were significantly reduced in PHPT (1.19 ± 0.10) compared to C (1.24 ± 0.09, p<0.01). Patients and controls did not differ for age, years since menopause (YSM), BMI, 25(OH)D serum levels, creatinine clearance, LS-BMD and FN-BMD. On the contrary, mean BMD values at both TH and R were significantly lower in PHPT patients compared to controls (p<0.01 and p<0.0001, respectively). In PHPT with vertebral fractures (VF+, n=29) TBS was significantly lower than in those without fracture (VF-, n=44)(1.14 ± 0.10 vs. 1.22 ± 0.10, respectively; p<0.01), whose TBS values did not differ from C. Mean TBS values in patients with (n=18) and without (n=55) non-vertebral fractures did not significantly differ (1.16 ± 0.09 vs. 1.20 ± 0.11). The presence of vertebral fractures was independently associated with the reduction of TBS (OR=0.003, 95% CI=0-0.534, p=0.028) and with YSM (OR=1.076, 95% CI=1.017-1.139, p=0.011), but not with age, the reduction of LS-BMD and the increase of BMI. The combination of YSM > 10 years plus TBS < 1.2 was associated with a significant risk of VF (OR=11.73, 95% CI 2.43-66.55, p<0.001). A TBS value <1.2 showed a better performance in individuating VF (sensibility 79.3%, specificity 61.4%, positive predictive value 57.5%, and negative predictive value 81.8%) in respect to YSM > 10 years. CONCLUSIONS: TBS seems to indirectly reflect an alteration of bone micro-architecture in postmenopausal women with PHPT.

The combination of FRAX and Ageing Male Symptoms scale better identifies treated HIV males at risk for major fracture.

OBJECTIVE: Osteoporosis and hypogonadism are common in men with HIV infection. Ageing Male Symptoms (AMS) scale measures symptoms related to hypogonadism. FRAX provides 10-year probability of major fractures. We investigated the role of AMS scale combined with FRAX without bone mineral density (BMD), in identifying HIV men with bone fragility. DESIGN: Cross-sectional observational study. METHODS: Fifty HIV-positive men treated with highly active antiretroviral therapy and 27 controls underwent hormonal evaluation, BMD scan and spine X-ray. The AMS questionnaire was administered. RESULTS: Osteoporosis was found in 24·0% of HIV patients and in 3·7% of controls (P = 0·05). In HIV patients, 9 radiological vertebral fractures were found (none in controls, P = 0·04). Calculated free testosterone suggested hypogonadism in 26% of HIV patients vs 4% of controls (P = 0·04); an abnormal AMS score (≥27) was found in 62% HIV patients compared with 41% controls (P = 0·04). ROC curves showed that FRAX for major fracture had a 23% sensitivity and a 100% specificity in identifying HIV patients with bone fragility (P = 0·002, with the threshold of 7% at which bisphosphonate therapy is cost-effective). Considering a value of AMS ≥27, we obtained an 82·6% sensitivity and a 42·9% specificity (P = 0·04). The combination of AMS and FRAX score achieved a 77·3% sensitivity and a 69% specificity (P = 0·02, cut-off 34). CONCLUSION: Combination of FRAX (without BMD) and AMS improved sensitivity of FRAX alone in identifying HIV patients at fracture risk, at the expense of reduced specificity.

Metabolic changes following 500 µg monthly administration of calcidiol: a study in normal females.

This study was performed to investigate the effect of monthly oral administration of 500 µg of calcidiol (25-hydroxyvitamin D(3)) for 4 months on both serum vitamin D levels and sequential changes of parameters of calcium metabolism; 18 normal women aged 24-72 years were investigated. There was a significant increase of serum 25(OH)D after the first administration; thereafter all values persisted significantly higher compared to the basal value (P < 0.001). Mean 1,25(OH)(2)D serum levels peaked at day 3 and then tended to stabilize following day 30. During the first month, all mean values observed following the initial administration were significantly higher than basal values. The first calcidiol dose produced a significant reduction of serum PTH levels (P < 0.001), which then remained constant over time. Concerning serum calcium and phosphorus, we were not able to demonstrate any significant change during the entire observation period. Considering the single values for both serum ionized and total calcium, the values of Ca(2+) exceeded upper limits of normal on only two occasions. Regarding biochemical markers of bone remodeling, mean changes of serum bone isoenzyme of alkaline phosphatase activity showed a significant trend to decrease, starting at day 30. No significant changes of serum CTX values were noted. Overall, 24-h urinary excretion of calcium did not change, seven values exceeding the threshold of 4 mg/kg body weight. Monthly administration of 500 µg of 25-hydroxyvitamin D(3) may be considered an alternative for vitamin D repletion, without any detrimental effect.

Secondary osteoporosis in men and women: clinical challenge of an unresolved issue.

OBJECTIVE: To evaluate the clinical and etiological factors of osteoporosis. We also tested the FRAX algorithm to compare the assessment of fracture risk in patients with primary or secondary osteoporosis. METHODS: A prospective study carried out in a large sample of 123 men and 246 women. All subjects had a biochemical, densitometric, and radiological examination of thoracic and lumbar spine. RESULTS: The prevalence of primary (men 52.9% vs women 50%; p = nonsignificant) and secondary (men 21.1% vs women 17.5%; p = nonsignificant) osteoporosis did not differ between the sexes. In contrast, the prevalence of primary osteoporosis was significantly higher than secondary causes (p < 0.0001) in both men and women. While women came to our attention for prevention of osteoporosis, men sought help because of clinical symptoms or disease-related complications, such as fractures. As evaluated by the FRAX tool, patients with osteopenia do not need treatment, in agreement with Italian guidelines. The estimated risk of major osteoporotic and hip fractures was significantly higher in women with secondary osteoporosis compared to men and also compared to women with primary osteoporosis. CONCLUSION: The prevalence of secondary osteoporosis in men is similar to that in women and it is less frequent than commonly reported. In patients with secondary osteoporosis, FRAX calculation may provide an estimate of a particularly high fracture risk in patients whose bone fragility is usually attributed to another disease.

Sex hormones and bone health in males.

Sex steroids play a key role in maintaining skeletal integrity lifelong, through a complex variety of endocrine, but also paracrine and possibly autocrine actions. The current knowledge that androgens may act as pro-hormones for estrogens has seriously challenged many traditional views, so that, at least for their skeletal actions, these can no longer be considered exclusively "male" or "female" hormones.