Osteoporosis in Healthy South Indian Males and the Influence of Life Style Factors and Vitamin D Status on Bone Mineral Density

Objective. To study the prevalence of osteoporosis and vitamin D deficiency in healthy men and to explore the influence of various life style factors on bone mineral density (BMD) and also to look at number of subjects warranting treatment. Methods. Ambulatory south Indian men aged above 50 were recruited by cluster random sampling. The physical activity, risk factors in the FRAX tool, BMD, vitamin D, and PTH were assessed. The number of people needing treatment was calculated, which included subjects with osteoporosis and osteopenia with 10-year probability of major osteoporotic fracture >20 percent and hip fracture >3 percent in FRAX India. Results. A total of 252 men with a mean age of 58 years were studied. The prevalence of osteoporosis and osteopenia at any one site was 20% (50/252) and 58%, respectively. Vitamin D deficiency (<20 ng/dL) was seen in 53%. On multiple logistic regression, BMI (OR 0.3; P value = 0.04) and physical activity (OR 0.4; P value < 0.001) had protective effect on BMD. Twenty-five percent warranted treatment. Conclusions. A significantly large proportion of south Indian men had osteoporosis and vitamin D deficiency. Further interventional studies are needed to look at reduction in end points like fractures in these subjects

Efficacy and safety of once-monthly pasireotide in Cushing's disease: A 12 month clinical trial

© 2017 Elsevier Ltd. Background: Cushing's disease is a rare debilitating endocrine disorder for which few prospective interventional studies have been done. We report results of the first phase 3 trial assessing long-acting intramuscular pasireotide in patients with Cushing's disease. Methods: In this phase 3 clinical trial we recruited patients aged 18 years or older with persistent, recurrent, or de-novo (non-surgical candidates) Cushing's disease who had a mean urinary free cortisol (mUFC) concentration (from three 24 h samples) of 1·5-5·0 times the upper limit of normal (ULN), a normal or greater than normal morning plasma adrenocorticotropic hormone concentration, and a pituitary source of Cushing's syndrome, from 57 sites across 19 countries. Exclusion criteria included previous pasireotide treatment, mitotane therapy within 6 months, and pituitary irradiation within 10 years. We randomly allocated patients 1:1 (block size of four) using an interactive-response-technology system to intramuscular pasireotide 10 mg or 30 mg every 4 weeks for 12 months (in the core phase). We stratified randomisation by screening mUFC concentration (1·5 to < 2·0 × ULN and 2·0-5·0 × ULN). The dose could be uptitrated (from 10 mg to 30 mg or from 30 mg to 40 mg) at month 4 if the mUFC concentration was greater than 1·5 × ULN, and at month 7, month 9, or month 12 if the mUFC concentration was greater than 1·0 × ULN. Investigators, patients, site personnel, and those assessing outcomes were masked to dose group allocation. The primary endpoint was the proportion of patients in each group with an mUFC concentration of less than or equal to the ULN at month 7. Efficacy analyses were based on intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01374906. Findings: Between Dec 28, 2011, and Dec 9, 2014, we randomly allocated 150 patients to receive pasireotide 10 mg (74 [49%] patients) or 30 mg (76 [51%] patients). The primary efficacy endpoint was met by 31 (41·9% [95% CI 30·5-53·9]) of 74 patients in the 10 mg group and 31 (40·8% [29·7-52·7] ) of 76 in the 30 mg group. The most common adverse events were hyperglycaemia (36 [49%] in the 10 mg group and 36 [47%] in the 30 mg group), diarrhoea (26 [35%] and 33 [43%] ), cholelithiasis (15 [20%] and 34 [45%] ), diabetes mellitus (14 [19%] and 18 [24%] ), and nausea (15 [20%] and 16 [21%] ). Serious adverse events suspected to be study drug related were reported in eight (11%) patients in the 10 mg group and four (5%) in the 30 mg group. Two (3%) patients in the 30 mg group died during the study (pulmonary artery thrombosis and cardiorespiratory failure); neither death was judged to be related to the study drug. Interpretation: Long-acting pasireotide normalised mUFC concentration in about 40% of patients with Cushing's disease at month 7 and had a similar safety profile to that of twice-daily subcutaneous pasireotide. Long-acting pasireotide is an efficacious treatment option for some patients with Cushing's disease who have persistent or recurrent disease after initial surgery or are not surgical candidates, and provides a convenient monthly administration schedule. Funding: Novartis Pharma AG

Influence of different reference databases on categorization of bone mineral density: A study on rural postmenopausal women from Southern India

Background and Objectives: Currently available DXA (Dual energy X-ray Absorptiometry) scanners utilise bone mineral density (BMD) of Caucasian population to calculate T scores and categorise BMD. We studied the influence of various databases on classification of BMD in south-Indian postmenopausal women aged above 50 years. Methodology: This was a cross-sectional study. Hologic DXA scanner was used to estimate BMD at lumbar spine (LS) and femoral neck (FN). T scores of ≤-2.5, -2.4 to -1, -0.9 to +1 were diagnostic of osteoporosis, osteopenia and normal respectively. Three reference databases(Italian, Korean and north Indian) were used to recalculate T scores. The agreement (K=kappa) between manufacturer provided database and the other databases was studied. The impact of different databases in diagnosing osteoporosis in subjects with FN fracture was assessed. Results: A total of 1956 postmenopausal women with mean (SD) age of 62 (4.3) years and 211 femoral neck(FN) fracture subjects with mean(SD) age of 68 (7.2) years were recruited. In subjects with fracture, osteoporosis at FN was found in 72% with Caucasian, 88% with North Indian, 56% with Italian, and 45% with Korean database. On comparing manufacturer provided database with the other population-specific reference, there was perfect agreement with north Indian (κ = 0.81 [FN], κ = 0.82 [LS]) and good agreement with the Italian database (κ = 0.78 [FN], κ = 0.74 [LS]). Conclusion: North-Indian database identified most of the participants with FN fracture as having osteoporosis and had perfect agreement with the manufacturer's database. Follow up studies will further validate the impact of utilizing this database in clinical practice

Osteoporosis knowledge and beliefs among postmenopausal women: A cross-sectional study from a teaching hospital in southern India

Objectives: Osteoporosis continues to be underrecognized in many parts of India. This study was undertaken to assess the level of knowledge of osteoporosis among postmenopausal women referred for a dual-energy X-ray absorptiometry (DXA) scan in a teaching hospital in southern India. Methodology: This cross-sectional study assessed the state of awareness in consecutive postmenopausal women referred for a DXA scan using a validated questionnaire – Osteoporosis Knowledge Assessment Tool. The proportion of correct responses was expressed as percentages. The mean scores obtained were also compared between different educational groups. Results: A total of 302 consecutive postmenopausal women who were referred for DXA participated in this study. The mean (standard deviation) age of the postmenopausal women included in this study was 58.8 (6) years. Although most subjects were aware of the consequences of osteoporosis, there was generalized lack of awareness with regard to risk factors and available treatment options. Overall about 60% had poor awareness about osteoporosis. Conclusion: This study showed a gross deficit in awareness of osteoporosis in Indian postmenopausal women. There is a need to prioritize on designing appropriate awareness campaigns in subjects at risk, according to their level of literacy

Detailed diagrammatic algorithm of the study with flow chart of NGS screening of the subject.

<p>Detailed diagrammatic algorithm of the study with flow chart of NGS screening of the subject.</p

Comprehensive Maturity Onset Diabetes of the Young (MODY) Gene Screening in Pregnant Women with Diabetes in India

<div><p>Pregnant women with diabetes may have underlying beta cell dysfunction due to mutations/rare variants in genes associated with Maturity Onset Diabetes of the Young (MODY). MODY gene screening would reveal those women genetically predisposed and previously unrecognized with a monogenic form of diabetes for further clinical management, family screening and genetic counselling. However, there are minimal data available on MODY gene variants in pregnant women with diabetes from India. In this study, utilizing the Next generation sequencing (NGS) based protocol fifty subjects were screened for variants in a panel of thirteen MODY genes. Of these subjects 18% (9/50) were positive for definite or likely pathogenic or uncertain MODY variants. The majority of these variants was identified in subjects with autosomal dominant family history, of whom five were in women with pre-GDM and four with overt-GDM. The identified variants included one patient with <i>HNF1A</i> Ser3Cys, two <i>PDX1</i> Glu224Lys, His94Gln, two <i>NEUROD1</i> Glu59Gln, Phe318Ser, one <i>INS</i> Gly44Arg, one <i>GCK</i>, <i>one ABCC8</i> Arg620Cys and one <i>BLK</i> Val418Met variants. In addition, three of the seven offspring screened were positive for the identified variant. These identified variants were further confirmed by Sanger sequencing. In conclusion, these findings in pregnant women with diabetes, imply that a proportion of GDM patients with autosomal dominant family history may have MODY. Further NGS based comprehensive studies with larger samples are required to confirm these finding</p></div

Detailed pedigree charts of MODY positive pregnant women with diabetes.

<p>Detailed pedigree charts of MODY positive pregnant women with diabetes.</p