The prevalence of vertebral fractures among Indian perimenopausal women and its association with ovarian biomarkers.

INTRODUCTION: There is dearth of data on prevalent vertebral fractures in perimenopausal women in India and limited literature on the utility of FSH, AMH and estradiol in evaluating bone health them. The objective was to study the prevalence of vertebral fractures (VF) and to assess the utility of FSH, estradiol and AMH in predicting them in Indian perimenopausal women MATERIALS AND METHODS: It was a cross-sectional study. Perimenopausal women aged 40-49 years underwent assessment for prevalent vertebral fractures, bone mineral density (BMD) and trabecular bone score (TBS). Utility of serum FSH, estradiol and AMH in predicting prevalent vertebral fractures was also assessed. RESULTS: A total of 300 perimenopausal women with mean (SD) age of 43.2 (2.8) years was recruited and 18% had moderate-severe VF. Mean (SD) serum AMH was lower in perimenopausal women with VF as compared to those without fractures [0.752 (0.594) vs 1.023 (0.704) P = 0.006]. AMH showed significant positive correlation with TBS (r = 0.3; P < 0.001) and BMD at the femoral neck (r = 0.2; P < 0.001) and lumbar spine (r = 0.3; P < 0.001).On ROC analysis, AMH demonstrated good performance in predicting prevalent VF with an AUC of 0.800 (95% CI 0.705-0.880) and a sensitivity of 85% and specificity of 60% at a cut-off of 1.12 ng/mL. On an exploratory multivariate logistic regression analysis, AMH significantly predicted prevalent fractures with an adjusted OR (OR) of 1.85 (95% CI: 1.03-3.00; P = 0.04). The performance of FSH and estradiol in predicting prevalent fractures was sub-optimal. CONCLUSION: About one-fifth of the study subjects had prevalent vertebral fractures. AMH may be a menstrual cycle independent biomarker and may reflect bone loss in perimenopausal women. Further prospective studies are needed to validate these findings.

Proximal Hip Geometry, Trabecular Bone Score, Bone Mineral Density and Bone Mineral Parameters in Patients With Cryptogenic and Hepatitis B Related Cirrhosis- A Study From the Indian Subcontinent.

The impact of cryptogenic cirrhosis on skeleton has not been studied in Indian context. So this study investigated bone health in male patients with early cryptogenic cirrhosis as defined by Child-Turcot-Pugh A (CTP-A) categorization and compared it with patients diagnosed to have hepatitis B related chronic liver disease (CLD) on treatment and age, sex-matched healthy controls. It was a cross-sectional study, in which thirty male subjects were recruited in each group. Bone mineral density (BMD), trabecular bone score (TBS), hip structural analysis (HSA) and bone mineral parameters were assessed. The mean ±SD age of the study subjects was 39.3 ± 9.2 years. The mean 25-hydroxy vitamin D was significantly lower in subjects with cryptogenic cirrhosis as compared to controls (p = 0.001). Subjects with cryptogenic cirrhosis had significantly lower (1.297 ± 0.099) TBS as compared to hepatitis-B related CLD (1.350 ± 0.094) control subjects (1.351 ± 0.088) (p = 0.04). BMD at the hip and lumbar spine was also significantly lower in subjects with cryptogenic cirrhosis as compared to hepatitis-B related CLD and healthy age matched controls (p < 0.05). Most components of HSA were significantly affected in subjects with cryptogenic cirrhosis as compared to control subjects (p < 0.05). Patients with cryptogenic cirrhosis had significantly low TBS and BMD lumbar spine and hip as well as poor proximal hip geometry which may be good predictor of future fragility fractures.

Distinct opposing associations of upper and lower body fat depots with metabolic and cardiovascular disease risk markers.

BACKGROUND: To examine the associations of total and regional adiposity with metabolic and cardiovascular disease (CVD) risk markers. METHODS: This cross-sectional study included 1080 (53.8% men, aged 39-44 years) individuals from South India. Anthropometry (height, weight, waist and hip circumference), body composition assessment using dual-energy X-ray absorptiometry (DXA), blood pressure (BP), and plasma glucose, insulin and lipids were measured. Regression analysis was used to examine associations of standardized fat measurements with type 2 diabetes (T2D), insulin resistance (IR), hypertension and hypertriglyceridemia and continuous measurements of BP, glucose, insulin, HOMA-IR and lipids. Contour plots were constructed to visualize the differential effect of upper and lower fat depots. RESULTS: DXA-measured fat depots were positively associated with metabolic and CVD risk markers. After adjusting for fat mass index, upper body fat remained positively, while lower body fat was negatively associated with risk markers. A one standard deviation (SD) increase in android fat showed higher odds ratios (ORs) for T2D (6.59; 95% CI 3.17, 13.70), IR (4.68; 95% CI 2.31, 9.50), hypertension (2.57; 95% CI 1.56, 4.25) and hypertriglyceridemia (6.39; 95% CI 3.46, 11.90) in men. A 1 SD increase in leg fat showed a protective effect with ORs for T2D (0.42; 95% CI 0.24, 0.74), IR (0.31; 95% CI 0.17, 0.57) and hypertriglyceridemia (0.61; 95% CI 0.38, 0.98). The magnitude of the effect was greater with DXA-measured fat compared with anthropometry. CONCLUSION: At any level of total body fat, upper and lower body fat depots demonstrate opposite risk associations with metabolic and CVD risk markers in Asian Indians.

Do Bone Density, Bone Microarchitecture, and Body Composition Differ in Recipients of Allogeneic Hematopoietic Stem Cell Transplant? A Cross-Sectional Study from Southern India.

The significant advancements made in the field of allogeneic hematopoietic stem cell transplantation (allo-HSCT) have ensured increased longevity in transplant recipients. However, they do have late effects that may adversely affect the endocrine system, bone health, and body composition. This study was undertaken to evaluate bone mineral density (BMD), trabecular bone score, and body composition in recipients of allo-HSCT and compare them with age, sex, and body mass index (BMI) matched controls. This was a cross-sectional study done in 63 cases and 65 matched controls. The mean femoral neck BMD was found to be lower in cases than in controls (0.777 [0.119] versus 0.846 [0.122] g/cm2, P =  .002). Among cases, the mean BMD at the neck of femur was lower in patients who had received myeloablative conditioning compared with those who had received the nonmyeloablative regimen (0.731 [0.090] versus 0.802 [0.126] g/cm2, P = .014]. The mean (SD) bone density at the lumbar spine was significantly lower in the group that had received total body irradiation compared with the group that did not (0.930 [0.111] versus 0.993 [0.127], P = .044). Trabecular bone score did not differ between cases and controls (1.383 [0.877] versus 1.389 [0.750], P = .670). The lean mass was significantly lower (15.9 [2.4] versus 18.6 [4.8] kg/m2, P < .001) and the prevalence of sarcopenia (42% versus 11%, P < .001) significantly higher in cases than in controls. Normal-weight obesity was also noted to be higher among those with sarcopenia than in those without (12/26 versus 5/36; P = .009). The procedure of allo-HSCT may thus cause an impairment of bone health and alterations in body composition well after the cure of the primary disease.

Platelet-Lymphocyte Ratio as a Novel Surrogate Marker to Differentiate Thyrotoxic Patients with Graves Disease from Subacute Thyroiditis: a Cross-Sectional Study from South India.

OBJECTIVE: Graves disease (GD) and the toxic phase of subacute thyroiditis (SAT) have similar clinical and biochemical presentations, and differentiating them requires sophisticated investigations. Since thyroid hormones have been noted to affect all hematologic cell lines, we have used the platelet lymphocyte ratio (PLR)-an index usually utilized in inflammatory or malignant disorders-to compare patients with and without thyrotoxicosis and to analyze its use in distinguishing between patients with GD and SAT prior to therapy. METHODS: This was a cross-sectional study conducted in the Department of Endocrinology, Christian Medical College, Vellore, India. During the study period, 800 patients with features of thyrotoxicosis visited the outpatient clinic. Those who had thyroid radioiodine (131I) uptake (RAIU) study and complete blood count (CBC) at diagnosis were included (N = 500). Based on the RAIU values, these were divided as GD (n = 354) and SAT (n = 146). Baseline characteristics, thyroid function tests, and components of the CBC and PLR were obtained. The data were compared with a group of 250 matched euthyroid controls. Analyses were performed using SPSS version 21.0 software. RESULTS: PLR showed significant reductions in both GD and SAT patients when compared to euthyroid controls (P = .01), with greater reductions seen in GD than SAT (74.5 ± 19 vs. 84.4 ± 26; P = .01). Using receiver operating characteristic analysis of PLR, an optimal PLR cut-off of 70.4 was found to differentiate GD from SAT with a sensitivity of 86% and specificity of 74%. CONCLUSION: PLR can be used as a novel surrogate marker to differentiate between patients with GD and SAT prior to therapy, especially in resource-limited settings.

Use of Gla-100 in Special Situations.

Insulin therapy is the cornerstone of diabetes management in people with type 2 diabetes mellitus (T2DM). Therefore, its use is recommended even in special populations and situations such as the elderly, pregnant women, obese individuals, people observing religious fasting, and in the presence of comorbidities such as renal insufficiency, and cancer. Since these special situations predispose to complications such as a high risk of hypoglycemia, patients need constant glucose monitoring and insulin dose adjustments, wherever applicable. This review discusses the various considerations that might guide the decision-making process in the special situations alluded to here. It also throws light on how insulin glargine 100 U/mL has emerged as a preferred choice of insulin therapy in most of these situations, on the strength of its inherently low hypoglycemia and weight gain potential, which has found traction even in the recent diabetes guidelines.

Renal Tubular Function, Bone Health and Body Composition in Wilson's Disease: A Cross-Sectional Study from India.

There is limited literature from India with regard to the prevalence and magnitude of renal tubular and bone manifestations in Wilson's disease (WD). Thus, we studied the prevalence of renal tubular acidosis among Indian patients with WD and also evaluated bone health and body composition in them. It was a cross-sectional study conducted at a south Indian tertiary care center. Twenty-five consecutive patients with WD aged more than 12 years attending the hepatology and neurology departments and 50 age, sex and BMI-matched controls were recruited. After clinical assessment, they underwent biochemical testing to assess renal tubular dysfunction. Bone mineral density (BMD) and body composition were assessed using a dual energy X-ray absorptiometry (DXA) scanner. Fifty-six percent (14/25) of patients with WD had renal tubular acidosis (RTA). Of them, 24% were diagnosed to have distal RTA. RTA was more common in hepatic WD patients who had prolonged duration of illness. Patients with WD had significantly lower BMD as compared to control subjects (p < 0.05). Low BMI, low IGF-1 and a shorter duration of therapy were key determinants of low bone mass in them (p < 0.05). Patients with WD had significantly more body fat (p = 0.01) and lower lean muscle mass (p = 0.03) when compared to age, sex and BMI-matched controls. In conclusion, renal tubular acidosis was common in patients with Wilson's disease. These patients had a lower bone mineral density, higher body fat percentage and lower lean muscle mass as compared to controls.

Ethnicity-specific cut-offs that predict co-morbidities: the way forward for optimal utility of obesity indicators.

Obesity indicators are useful clinical tools in the measurement of obesity, but it is important for clinicians to appropriately interpret their values in individuals with different ethnicities. Future research is needed to identify optimal cut-offs that can predict the occurrence of cardio-metabolic comorbidities in individuals of different ethnic descent. Assessment of more recently developed indicators like the Edmonton Obesity Staging System and visceral adipose tissue are able to appropriately identify metabolically at-risk individuals.

The BMI-adiposity conundrum in South Asian populations: need for further research.

High body fat in apparently lean individuals is a commonly described phenotype in individuals of Asian descent, but very limited consolidated scientific literature is available on this topic. This phenotype is known as 'normal-weight obesity' and may explain the large disparity between the prevalence of obesity (as measured by BMI) and diabetes that occurs in these individuals. Routine use of obesity indicators that best predict body fat content would help to identify these individuals in clinical practice. In this debate, we would like to highlight that even though fat and BMI have a good correlation, as suggested by Kryst et al. (2019), clinicians, public health researchers and policymakers should consider the use of these indicators in conjunction with each other rather than individually. Future research is needed on pathogenic mechanisms, diagnostic modalities and therapeutic options in these individuals which will help to further characterize and manage these patients appropriately.

Evaluation of Different Screening Tools for Predicting Femoral Neck Osteoporosis in Rural South Indian Postmenopausal Women.

The measurement of bone mineral density by dual-energy X-ray absorptiometry scan is the "gold standard" for the diagnosis of osteoporosis, which has limited availability in many parts of India. This study was done to assess the diagnostic performance of 6 internationally validated tools (Simple Calculated Osteoporosis Risk Estimation [SCORE], age, bulk, one or never estrogen [ABONE], Osteoporosis Risk Assessment Instrument [ORAI] and Osteoporosis Self-Assessment Tool for Asians [OSTA], Fracture Risk Assessment Tool [FRAX®], and calcaneal quantitative ultrasound [QUS]) for the diagnosis of osteoporosis at the femoral neck (FN). This was a cross-sectional study conducted in 2108 ambulatory South Indian rural postmenopausal women who were assessed with SCORE, ABONE, ORAI, OSTA, and FRAX® tools. QUS was performed in 850 subjects. Bone mineral density was estimated by dual-energy X-ray absorptiometry scan at the FN, and sensitivity and specificity were calculated for all tools for predicting FN osteoporosis. The receiver operating characteristic curve was constructed for each tool and the area under the curve (AUC) was calculated. FN osteoporosis was seen in 27%. The sensitivities of SCORE, ABONE, OSTA, ORAI, FRAX®, and QUS were 91.3%, 91.0%, 88.5%, 81.0%, 72.7%, and 81.9%, and the specificities were 36.0%, 33.5%, 41.7%, 52.0%, 60.5%, and 50.3%, respectively, for the FN osteoporosis. When the receiver operating characteristics were constructed, the AUC was good only for SCORE (0.806), and the performance of the rest was under fair category (0.713-0.766). In our large cohort of rural postmenopausal women, the SCORE screening tool was found to be useful with good sensitivity and good AUC for predicting FN osteoporosis. Thus, this tool may be used in resource-limited countries to screen the population at risk and to enable treating physicians to make appropriate management decisions.

The Role of Magnesium in Post-thyroidectomy Hypocalcemia.

BACKGROUND: The purpose of this study was to determine the prevalence of hypomagnesemia in patients undergoing thyroidectomy and evaluate the relationship of hypomagnesemia with transient and severe hypocalcemia. MATERIALS AND METHODS: This was a prospective observational study of 50 patients undergoing thyroidectomy. Blood samples were collected pre- and postoperatively for calcium, albumin, magnesium, phosphorous and parathormone (PTH). Signs, symptoms of hypocalcemia and volume of intravenous fluids used perioperatively were documented. The statistical analysis was performed using STATA I/C 10.1. RESULTS: Preoperatively, twelve patients (24 %) had hypomagnesemia and one (2 %) hypocalcemia. On the first postoperative day, hypomagnesemia was seen in 70 % and hypocalcemia in 30 %. A similar trend was observed in the fall and rise of postoperative calcium and magnesium values (p = 0.41). Severe hypocalcemia was present in three patients (6 %). All three patients had a very low postoperative PTH (<2 pg/ml). Among them, two patients (66 %) had hypomagnesemia and their hypocalcemia responded to intravenous magnesium correction. Significant risk factors for postoperative hypocalcemia include a higher volume of fluid used perioperatively and low postoperative PTH (<8 pg/ml) (p = 0.01 and 0.03, respectively). CONCLUSION: Preoperative hypomagnesemia (24 %) was prevalent in this cohort of patients. Postoperative hypomagnesemia is a common event (70 %) following total thyroidectomy, and magnesium levels tend to mimic the calcium levels postoperatively. The cause of hypocalcemia post-thyroidectomy in this study is mainly a factor of parathyroid function and fluid status. Severe hypocalcemia is a rare event, and hypomagnesemia is associated in the majority of these patients. The role of magnesium correction to alleviate severe hypocalcemia needs to be further studied.

The impact of the Hologic vs the ICMR database in diagnosis of osteoporosis among South Indian subjects.

BACKGROUND AND OBJECTIVES: Recently, the Indian Council of Medical Research (ICMR) has published normative data for bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) scanning. However, the impact this has had on the diagnosis of osteoporosis when compared to currently used Caucasian databases has not been analysed. Hence, this study was undertaken to look at agreement between the Hologic Database (HD) based on BMD normative data in Caucasians and the ICMR database (ICMRD) in defining osteoporosis in subjects with or without hip fracture. MATERIALS AND METHODS: It is a cross -sectional study of 2976 subjects (men 341, women 2757) (mean age ± SD = 62·2 ± 7·2 years), including 316 subjects with low impact hip fracture: 2199 were from the hospital database, and 461 were healthy postmenopausal women from the community who underwent (DXA) scanning between January 2010 and March 2013. Recalculated T scores from ICMRD were used for the diagnosis of osteoporosis and compared with HD. RESULTS: An almost perfect agreement existed between the two databases for the diagnosis of osteoporosis at the hip (κ -0·82, P < 0·0001) in all subjects, and a moderate relationship existed in those with hip fracture (κ -0·65, P < 0·0001). Seventy-three of 316 hip fracture subjects (23·5%) defined as osteoporosis according to HD were classified as osteopenia according to ICMRD. CONCLUSION: The threshold of hip BMDT score for treating osteoporosis may have to be redefined if the ICMR reference database is used. Initiation of treatment in these subjects must be based on multiple fracture risk factor assessment in addition to looking at BMD. Further studies with a larger sample size of subjects with fracture are needed to validate our findings.

Role of Genetic Testing in the Management of Indeterminate Thyroid Nodules in the Indian Setting.

The increased detection of thyroid nodules in the human population has led to an increase in the number of thyroid surgeries without an improvement in survival outcomes. Though the choice for surgery is straightforward in malignant thyroid nodules, the decision is far more complex in those nodules that get categorized into indeterminate thyroid nodules (ITN) by fine needle aspiration. Therefore, there is a pressing need to develop a tool that will aid in decision-making among the ITN. In this context, the development of various molecular testing (MT) panels has helped to confirm or rule out malignancy, reducing unnecessary surgeries and potentially guiding the extent of surgery as well. Currently, such tests are widely used among the Western population but these MT panels are not used by the South Asian population because of non-availability of validated panels and the high cost involved. There is a need to develop a suitable panel which is population-specific and validate the same. In this review, we would focus on current trends in the management of ITN among the South Asian population and how to develop a novel MT panel which is cost-effective, with high diagnostic accuracy obviating the need for expensive panels that already exist.

Tenofovir-induced hypophosphatemic osteomalacia: how do bone mineral density, trabecular bone score and proximal hip geometry change with treatment?

Summary: Tenofovir-induced osteomalacia secondary to proximal renal tubular dysfunction is not an uncommon complication known to occur. A 46-year-old woman was referred for the evaluation of osteoporosis which was diagnosed elsewhere. She had polyarthralgia, bony pains and proximal muscle weakness of 1 year duration. She was diagnosed to have HIV infection and was on antiretroviral therapy that consisted of tenofovir, lamivudine and efavirenz for the past 12 years. She had attained menopause 5 years back. On examination, she had bone tenderness, proximal myopathy and painful restriction of movement of her lower limbs. Investigations showed features of renal tubular acidosis, hypophosphatemia and raised alkaline phosphatase that were suggestive of osteomalacia. X-ray of the pelvis showed diffuse osteopenia and an MRI of the pelvis done showed multiple insufficiency fractures involving the head of femur on both sides. Following this, her tenofovir-based regimen was changed to abacavir, efavirenz and lamivudine with addition of neutral phosphate supplements and calcitriol. On follow-up after 6 months, she had significant improvement in her symptoms as well as in the bone mineral density at the lumbar spine (33.2%), femoral neck (27.6%), trabecular bone score (13.2%) and reduction in the buckling ratio at the narrow neck (6.3%), inter-trochanteric region (34%) and femoral shaft (28.8%). Tenofovir-induced osteomalacia is encountered in individuals on prolonged treatment with tenofovir. Treatment consists of changing to a non-tenofovir-based regimen, as well as supplementation of phosphate and calcitriol. Treatment results in remarkable improvement in symptoms and most densitometric indices. Learning points: Tenofovir is a nucleotide reverse transcriptase inhibitor (NRTI) and is a major drug in the treatment of retroviral and hepatitis B infections. Tenofovir-related hypophosphatemic osteomalacia is related to proximal tubulopathy and is not an uncommon occurrence. Treatment mandates changing to a non-tenofovir-based regimen with supplementation of neutral phosphate and calcitriol. Treatment results in a significant improvement in bone mineral density, trabecular bone score and hip geometric parameters.

Caring for the Bone Health Among Liver Transplant Recipients.

Liver transplant outcomes have improved over the years, and currently, the quality of life and long-term well-being of these patients needs to be improved. Improving bone health goes a long way toward achieving this objective. Poor bone health (osteopenia and osteoporosis) although prevalent, is often overlooked owing to its asymptomatic nature. It can be complicated by debilitating fracture affecting quality of life. It is recommended to assess and optimize bone health prior to liver transplant. Multiple factors contribute to poor bone health in a liver transplant recipient and it is vital to understand and ameliorate these. A careful and targeted approach with inputs from multidisciplinary team involving transplant physician, endocrinologist, occupational therapist, nutritionist, and nursing personnel may often be required. In this review, we aim to concisely discuss the various aspects related to prevalence, pathophysiology, evaluation, treatment, and follow-up of bone disease among liver transplant recipients.

Bone health in ambulatory male patients with chronic obstructive airway disease - A case control study from India.

Objective: Chronic obstructive airway disease (COPD) is characterized by airflow limitation due to airway and/or alveolar abnormalities with significant extra-pulmonary manifestations. Bone health impairment is an extra-pulmonary complication of COPD which is less well studied in India. Moreover, it can contribute to significant morbidity and mortality. Hence, we aim to estimate the prevalence of osteoporosis and metabolic parameters of adverse bone health in patients with COPD. Methods: In this case control study, male subjects aged 40-70 years with COPD attending the respiratory outpatient clinic in a tertiary care hospital were recruited over a period of 2 years and the control population were derived from the historical cohort who were apparently healthy with no obvious diseases. Metabolic parameters of bone health measured from fasting blood samples were calcium, albumin, alkaline phosphatase, phosphorous, parathormone, creatinine, 25-hydroxy vitamin D, and testosterone. Bone mineral density (BMD) was estimated using DXA scan and the World Health Organization (WHO) criteria was used to categorize into osteoporosis, osteopenia, and normal BMD based on the T-score at femoral neck, lumbar spine and distal forearm. Pulmonary function tests and 6 minute walk test were performed if they had not been done in the previous 3 months. The associations of COPD with osteoporosis were analyzed using linear regression analysis and effect size are presented as beta with 95% confidence interval. Results: Of the 67 participants with COPD enrolled in the study, osteoporosis was present in 61% (41/67) and osteopenia in an additional 33% (22/67) of the cases, which was higher when compared to the control population (osteoporosis 20% [50/252] and osteopenia 58% [146/252]). In regression modeling, there was a trend toward adverse bone health with advanced age, low body mass index, low forced expiratory volume in 1 second and testosterone deficiency in COPD. Conclusion: Individuals with COPD have a substantially higher prevalence of osteoporosis and osteopenia, up to almost twice that of the general population, with a significant number demonstrating at least one parameter of adverse metabolic bone health on assessment. Hence, bone health assessment should be a part of comprehensive COPD care to prevent adverse consequences due to poor bone health.