Heterogeneity in regional changes in body composition induced by androgen deprivation therapy in prostate cancer patients: potential impact on bone health-the BLADE study.

BACKGROUND: It is not clear whether changes in body composition induced by androgen deprivation therapy (ADT) in prostate cancer (PC) patients are uniform or vary in the different body districts and whether regional lean body mass (LBM) and fat body mass (FBM) could have an impact on bone health. OBJECTIVE: To prospectively evaluate the regional changes in LBM and FBM in PC patients submitted to degarelix; to explore the relationship of regional body composition and bone mineral density (BMD) and bone turnover markers. DESIGN, SETTING, AND PARTICIPANTS: 29 consecutive non metastatic PC patients enrolled from 2017 to 2019. FBM, LBM and bone mineral density (BMD) evaluated by dual-energy x-ray absorptiometry (DXA) at baseline and after 12-month of ADT. Alkaline phosphate (ALP) and C-terminal telopeptide of type I collagen (CTX) assessed at baseline, 6 and 12 months. INTERVENTION: All patients underwent degarelix administration. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: T-test or sign test and Pearson or Spearman test for continuous variables were used when indicated. RESULTS AND LIMITATIONS: Median percent increase in FBM ranged from + 14.5% in trunk to + 25.4% in the left leg after degarelix. LBM changes varied from + 2% in the trunk to - 4.9% in the right arm. LBM in both arms and legs and their variations after degarelix directly correlated with ALP and inversely correlated with CTX. Lean mass of limbs, trunk and legs significantly correlated with BMD of the hip, lean mass of the trunk significantly correlated with spine BMD. These are post-hoc analysis of a prospective study and this is the main limitation. CONCLUSIONS: an heterogeneous change in body composition among body district is observed after ADT and bone turnover is influenced by lean mass and its variation. A supervised physical activity is crucial to maintain general physical performance and preserving bone health.

Impact of hypogonadism on bone mineral density and vertebral fractures in HIV-infected men.

PURPOSE: Hypogonadism and osteoporosis are frequently reported in HIV-infected men and, besides multifactorial pathogenesis, they might be directly linked because of testicular involvement in bone health. We evaluated the prevalence of osteoporosis and vertebral fractures (VFs) in HIV-infected men, and assessed their relationship with gonadal function. METHODS: We enrolled 168 HIV-infected men (median age 53). Osteoporosis and osteopenia were defined with T-score ≤ - 2.5SD and T-score between - 1 and - 2.5SD, respectively. VFs were assessed by quantitative morphometric analysis. Total testosterone (TT), calculated free testosterone (cFT), Sex Hormone Binding Globulin (SHBG), Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) were obtained; overt hypogonadism was defined on symptoms and low TT or cFT, and classified into primary and secondary according to gonadotropins; compensated hypogonadism was defined as normal TT and cFT with high LH levels. RESULTS: Overall, osteoporosis and osteopenia were found in 87.5% of patients, and VFs were detected in 25% of them; hypogonadism was identified in 26.2% of cases. Osteoporotic patients had higher SHBG vs those with normal bone mineral density (BMD). Fractured patients were more frequently hypogonadal and with higher SHBG. SHBG showed negative correlation with both spine and femoral BMD, and positive correlation with VFs. In multivariate models, FSH showed negative impact only on femoral BMD, whereas older age and higher SHBG predicted VFs. CONCLUSION: We found a high burden of bone disease and hypogonadism in HIV-infected men, and we showed that the impact of gonadal function on bone health is more evident on VFs than on BMD.

Psycho-social characteristics in patients with discopathy: Quality of Life, coping strategy and mood state.

The pathologies of the musculoskeletal apparatus are the most common cause of chronic diseases, with a huge impact on people and society. Scientific literature has discovered how experiencing chronic pain directly affects peoples' well-being, lifestyle, social relationships and can also cause psychological distress. The present study aims to investigate pain experience in patients with hernias or protrusions of the cervical and lumbosacral tract on a sample of 120 patients, recruited from patients of Poliambulatorio Oberdan, medical centre in Brescia (Italy) specialized in physical rehabilitation and CT-guided oxygen ozone therapy. In a bio-psychosocial perspective, the research aimed to investigate how the perception of pain, the mood state associated with it, the coping strategies adopted and the quality of life differ according to each patient's gender and to the more or less prolonged use of pain medication. The data were collected by means of medical and psychological anamnestic interviews and self-report tests (WHOQOL-BREF, COPE-NVI, POMS). The quantitative analysis, carried out through SPSS 25 (2017) software, showed how functional impairment of one's autonomy (walking, driving) affects mood states. In particular, the female sample expressed a more deflected mood, despite the greater use of relational and/or transcendent support (coping strategies) compared to men. The study suggests that the greater impairment of the moods of women can be attributed both to the caregiving role they play, which often results in a greater fatigue and difficulties in redefining this role following the algic condition, and more general differences in the expression of suffering, which, on a cultural level, sees men emotionally coerced. The analysis also shows how taking pain medication for a long period of time has a negative impact on the quality of life. The results suggest that the patients treated with analgesic therapy tend to adopt avoidant coping styles, which usually escalate into postponement of the time when dealing with a stressful situation and, if used in the long run, may lead to worsening health condition.

How to improve effectiveness of pegvisomant treatment in acromegalic patients.

PURPOSE: Pegvisomant (PEGV) treatment in acromegaly patients resistant to somatostatin analogues is less effective in the real life than in clinical trials. This is a multicenter, observational, retrospective, longitudinal study. The aim was to detect characteristics which improve long-term PEGV effectiveness. METHODS: 87 acromegalic patients treated with PEGV have been enrolled in seven referral Italian centres. PEGV was administered for up to 4 years, at doses up titrated until IGF-1 normalization or to ≥ 30 mg/day. The rate of patients who reached IGF-1 normalization at last visit has been calculated. RESULTS: IGF-1 was normalized in 75.9% of patients after 1 year and in 89.6% at last visit. Disease control was associated with lower baseline GH, IGF-1 and IGF-1 xULN and was more frequent when baseline IGF-1 was < 2.7 × ULN (p < 0.02). PEGV dose was dependent on baseline IGF-1 > 2.7 × ULN (p < 0.05) and doses > 1.0 mg/BMI/day were administered more frequently when baseline IGF-1 was > 2.0 × ULN (p = 0.03). PEGV resistance was associated with higher BMI (p = 0.006) and was more frequent when BMI was > 30 kg/m2 (p = 0.07). There were no significant differences between patients treated with monotherapy or combined treatment. IGF-1 normalization, PEGV dose and rate of associated treatment were similar between males and females. PEGV effectiveness was independent from previous management. Diabetic patients needed higher doses of PEGV than non-diabetic ones. CONCLUSIONS: PEGV effectiveness improves when up titration is appropriate. Higher PEGV doses at start and a more rapid up-titration are necessary in patients with obesity and/or IGF-1 > 2.7 × ULN.

Diabetes in Cushing Disease.

PURPOSE OF REVIEW: This review focuses on the pathophysiological and clinical aspects of diabetes mellitus occurring in patients with Cushing disease (CD). RECENT FINDINGS: Insulin resistance and impairment in insulin secretion are both involved in the pathogenesis of glucocorticoid-induced diabetes. Correction of glucocorticoid excess does not always resolve abnormalities of glucose homeostasis, and correction of hyperglycaemia is specifically required. In fact, insulin resistance may persist even after correction of glucocorticoid excess and diabetes needs to be treated for long term. On the other hand, emerging drugs used in the treatment of CD, such as the novel somatostatin analog pasireotide, may have direct effects on glucose homeostasis regardless of control of cortisol excess. Diabetes mellitus is a frequent and early complication of CD with important diagnostic, prognostic and therapeutic implications. Specifically, diagnosis of CD in patients with diabetes may be difficult due to potential misinterpretation of markers of cortisol hypersecretion. Moreover, diabetes mellitus is often difficult to be controlled in CD requiring a careful and dedicated therapeutic approach. Finally, the coexistence of diabetes may influence the therapeutic decision making in CD, since drugs used in this setting may variably influence glucose homeostasis regardless of control of hypercortisolism.

Acromegalic osteopathy.

Acromegalic osteopathy is an emerging complication of acromegaly characterized by increase in bone turnover, deterioration in bone microarchitecture and high risk of vertebral fractures. Vertebral fractures, as diagnosed by a radiological and morphometric approach, occur in about one-third of acromegaly patients in close relationship with duration of active disease. However, the prediction of vertebral fractures in this clinical setting is still a matter of uncertainty, since the pathogenesis of acromegalic osteopathy is multifactorial and fractures may occur even in presence of normal bone mineral density. In this narrative article, we summarize the pathophysiology and clinical aspects of acromegalic osteopathy.

New medical therapies of acromegaly.

Acromegaly is a rare disease associated with significant morbidity and increased mortality. Treatment of acromegaly aims at controlling growth hormone hypersecretion, improving patients' symptoms and comorbidities and normalizing mortality. The therapeutic options for acromegaly include surgery, medical therapies and radiotherapy. However, despite all these treatment options, approximately one-half of patients are not adequately controlled. Progress in molecular research has made possible to develop new therapeutic strategies to improve control of acromegaly. This article will review the new medical approaches to acromegaly which consist in evolution of traditional therapeutic protocols and development of new molecules with different profiles of activity.

Role of bone mineral density in predicting morphometric vertebral fractures in patients with HIV infection.

UNLABELLED: This study investigated the bone of HIV patients both in terms of quantity and quality. It was found that HIV-infected patients did fracture independently of the degree of bone demineralization as in other forms of secondary osteoporosis. INTRODUCTION: We aimed to determine the prevalence of vertebral fractures (VFs) in HIV patients who were screened by bone mineral density (BMD) and to explore possible factors associated with VFs. METHODS: This is a cross-sectional study that included HIV-infected patients recruited in the Clinic of Infectious and Tropical Diseases and that underwent BMD measurement by dual-energy X-ray absorptiometry (DXA) at the lumbar spine and hip (Lunar Prodigy, GE Healthcare). For the assessment of VFs, anteroposterior and lateral X-ray examinations of the thoracic and lumbar spines were performed and were centrally digitized. Logistic regression models were used in the statistical analysis of factors associated with VFs. RESULTS: One hundred thirty-one consecutive patients with HIV infection (93 M, 38 F, median age 51 years; range, 36-75) underwent BMD measurement: 25.2 % of patients showed normal BMD, while 45 % were osteopenic and 29.7 % osteoporotic. Prevalence of low BMD (osteopenia and osteoporosis) was higher in females as compared to males (90 vs 69 %) with no significant correlation with age and body mass index. VFs occurred more frequently in patients with low BMD as compared to patients with normal BMD (88.5 vs. 11.4 %; p < 0.001) without any significant difference between osteopenia and osteoporosis (43 vs. 46 %; p = 0.073). VFs were significantly associated with older age and previous AIDS events. CONCLUSIONS: These results suggest a BMD <-1 threshold to identify patients at risk of skeletal fragility and, therefore, good candidates for morphometric evaluation of spine X-ray in line with other forms of secondary osteoporosis with impaired bone quality.

Outcome of glucose homeostasis in patients with glucocorticoid-induced osteoporosis undergoing treatment with bone active-drugs.

Over the last few years, there has been experimental evidence for the existence of cross-talking between bone remodeling and glucose metabolism. Whether this experimental model can be translated to humans is still debated, and it is also unclear whether the modulation of bone turnover by anti-osteoporotic drugs may lead to changes in glucose metabolism. The aim of this 12-month prospective study was to investigate whether treatment of glucocorticoid-induced osteoporosis (GIO) with bipshosphonates or teriparatide may influence serum glycated hemoglobin (HbA1c) and fasting plasma glucose. One-hundred-eleven patients (70 F, 41 M, median age 70, range: 55-89) chronically treated with glucocorticoids were evaluated for changes in serum HbA1c and fasting plasma glucose during treatment with bisphosphonates (45 cases) or teriparatide (33 cases) as compared to those occurring during treatment with calcium and vitamin D alone (33 cases). In patients treated with teriparatide, but not in those treated with bisphosphonates or calcium and vitamin D alone, a statistically significant (p=0.01) decrease in serum HbA1c was observed during the follow-up, the change being greater (p=0.01) in patients with diabetes as compared to those without diabetes. In most cases, the decrease of serum HbA1c was relatively limited and in some patients the improvement of glucose homeostasis was concomitant with implementation of anti-diabetic treatments. Fasting plasma glucose did not change significantly during either bisphosphonates or teriparatide treatments. In conclusion, currently used bone active drugs may produce limited effects on glucose metabolism in patients with GIO. Interestingly, the bone anabolic drug teriparatide was shown to be associated with some improvement in serum HbA1c in this clinical context.

Association between l-thyroxine treatment, GH deficiency, and radiological vertebral fractures in patients with adult-onset hypopituitarism.

OBJECTIVE: In this study, we aimed at evaluating the association between radiological vertebral fractures and levo-thyroxine (l-T4) replacement doses in adult patients with hypopituitarism. DESIGN: Cross-sectional study. METHODS: We studied 74 adult hypopituitary patients (males, 43; females, 31; mean age, 57 years; and range, 23-79) with central hypothyroidism treated with l-T4 (median daily dose: 1.1  µg/kg). All patients also had severe GH deficiency (GHD) and 38 of them were replaced with recombinant GH. Vertebral fractures were assessed by a quantitative morphometric analysis performed on thoracic and lumbar spine lateral X-ray. RESULTS: Radiological vertebral fractures were found in 23 patients (31.1%) in association with untreated GHD (P=0.02), higher serum free T4 levels (P=0.03), a higher daily dose of l-T4 (P=0.005), and a longer duration of hypopituitarism (P=0.05). When GHD was treated, the prevalence of vertebral fractures was more frequent (P=0.03) in patients receiving high l-T4 doses (third tertile: >1.35  µg/kg per day) as compared with patients who were treated with lower drug doses (first tertile: <0.93  µg/kg per day). Such a difference was not observed in patients with untreated GHD who showed a higher prevalence of vertebral fractures regardless of l-T4 daily doses. Multivariate analysis showed that untreated GHD (odds ratio: 4.27, 95% CI 1.27-14.33; P=0.01) and the daily dose of l-T4 (odds ratio: 4.01, 95% CI 1.16-14.39; P=0.03) maintained a significant and independent association with vertebral fractures in patients with central hypothyroidism. CONCLUSIONS: Our data suggest for the first time that a relative overtreatment with l-T4 may influence the fracture risk in some patients with hypopituitarism.

Vertebral fractures in patients with acromegaly: a 3-year prospective study.

CONTEXT: Cross-sectional studies showed an elevated prevalence of vertebral fractures in acromegaly. However, no data are available on incident vertebral fractures in this clinical setting. OBJECTIVE: The objective of the study was to investigate the incidence and risk factors of vertebral fractures in patients with acromegaly. DESIGN: This was a 3-year prospective study. SETTING: The study was conducted at referral centers. SUBJECTS: Eighty-eight patients with acromegaly (33 females, 55 males; mean age 50 years, range 21-85 years) and 106 control subjects, matched for sex and age (43 females and 63 males, mean age 55 years, range 33-79 years), attending outpatient bone clinics participated in the study. MAIN MEASURES: Patients and control subjects were evaluated for the incidence of vertebral fractures using a quantitative morphometric approach on spine x-ray, which was performed at baseline and after 3 years of follow-up. At the same time points, patients with acromegaly were also evaluated for bone mineral density with dual-energy X-ray absorptiometry at lumbar spine and femoral neck. RESULTS: After a 3-year follow-up, 37 patients with acromegaly (42.0%) and 4 control subjects (3.8%) experienced incident vertebral fractures (P < .001). The incidence of vertebral fractures was significantly higher in patients with active disease as compared with those who had controlled/cured acromegaly at the study entry (62.5% vs 25.0%; P < .001). The risk of incident vertebral fractures was significantly associated with hypogonadism, a change in the femoral neck bone mineral density, and prevalent vertebral fractures at the study entry only in patients with controlled/cured acromegaly, whereas in patients with active disease, the fracture risk was not influenced by the above-mentioned clinical factors, but it was significantly associated with the duration of active acromegaly. CONCLUSIONS: This prospective study demonstrates a high rate of incident vertebral fractures both in patients with active and controlled acromegaly.