Inherited fibroblast growth factor 23 excess.

Syndromes of inherited fibroblast growth factor 23 (FGF-23) excess encompass a wide spectrum that includes X-linked hypophosphataemia (XLH), autosomal dominant and recessive forms of rickets as well as various syndromic conditions namely fibrous dysplasia/McCune Albright syndrome, osteoglophonic dysplasia, Jansen's chondrodysplasia and cutaneous skeletal hypophosphataemia syndrome. A careful attention to patient symptomatology, family history and clinical features, supported by appropriate laboratory tests will help in making a diagnosis. A genetic screen may be done to confirm the diagnosis. While phosphate supplements and calcitriol continue to be the cornerstone of treatment, in recent times burosumab, the monoclonal antibody against FGF-23 has been approved for the treatment of children and adults with XLH. While health-related outcomes may be improved by ensuring adherence and compliance to prescribed treatment with a smooth transition to adult care, bony deformities may persist in some, and this would warrant surgical correction.

Bisphosphonate-induced atypical femoral fracture in tandem: long-term follow-up is warranted.

Summary: Although bisphosphonates (BPs) are mainly used for the treatment of osteoporosis and are generally safe, long-term use and more dosage as utilised in malignant conditions may be associated with the rare adverse event of an atypical femoral fracture (AFF). Occasionally, the risk of developing an AFF persists long after BPs are withdrawn. A 39-year-old woman who underwent chemotherapy and an autologous stem cell transplantation for multiple myeloma presented to us with history of pain in the left thigh. She had received multiple doses of oral and parenteral BPs for about 10 years in view of the underlying myeloma with osteoporosis. Her investigations showed a suppressed CTX of 192 pg/mL, and radiograph of pelvis displayed thickened cortices with beaking of the left femoral shaft, which was suggestive of an AFF. Following discontinuation of BPs, she underwent prophylactic intra-medullary nailing with which her symptoms improved. Five years later, she presented with similar complaints on the right side. Investigations showed that her bone turnover continued to be suppressed with Cross linked C- Telopeptide of type 1 collagen (CTX) of 165 pg/mL and an X-ray done showed AFF on the right side despite being off BPs. A second intra-medullary nailing was done and on follow-up, she has been symptom-free and independent in her daily activities. Discontinuation of BPs may not prevent the incident second AFF and, therefore, thus warranting long-term follow-up. Learning points: Regular screening and follow-up of patients who receive long-term bisphosphonate (BP) therapy should be done. Discontinuation of BPs does not preclude the possibility of repeated occurrence of a second AFF. Long-term BP therapy warrants regular monitoring and follow-up should an AFF occur.

Disrupted Sleep Architecture Is Associated With Incident Bone Loss in Indian Postmenopausal Women: A Prospective Study.

Inadequate sleep has been shown to be detrimental to several body systems, including the bone. We proposed to study the impact of insomnia on bone health in Indian postmenopausal women. In a 2-year prospective study, ambulant community-dwelling postmenopausal women aged >50 years were recruited through simple random sampling. Sleep duration was recorded based on self-reported sleep duration and sleep quality using the Women's Health Initiative Insomnia Rating Scale (WHIIRS). Anthropometry, bone biochemistry including bone turnover markers (C-terminal telopeptide of type 1 collagen [CTX], N-terminal telopeptide of type 1 pro-collagen [P1NP]), bone mineral density (BMD), and trabecular bone score (TBS) were assessed at baseline and at the end of 2 years. Among 190 postmenopausal women with mean (SD) age of 58.2 (6.9) years, 65/190 (34.2%) had insomnia (WHIIRS ≥ 9) and 20/190 (10.5%) developed osteoporosis at any site on follow-up. The percentage decline over 2 years in BMD in women with insomnia was significantly (p < 0.001) higher at femoral neck (2.9 [1.6] versus 1.2 [1.2]%) and lumbar spine (4.5 [2.0] versus 1.6 [1.1]%). The decrement in TBS was also significantly higher (p < 0.001) in women with suboptimal sleep (1.5 [2.1] versus 0.5 [1.0] %) when compared with those with adequate sleep. The increment in CTX (46.4 [32.2] versus 18.9 [26.4]) and decrement in P1NP (35.4 [9.1] versus 16.7 [18.9]), respectively, were also greater (p < 0.001) in women with insomnia compared with those without. On multivariate analysis, insomnia was the sole factor that was predictive (adjusted odds ratio [OR] = 9.3; 95% confidence interval [CI] 2.9-29.6; p < 0.001) of incident osteoporosis. In conclusion, poor sleep quality was associated with incident osteoporosis in Indian postmenopausal women. Optimal sleep may help to retard ongoing bone loss that results from sleep deprivation and requires further research. © 2022 American Society for Bone and Mineral Research (ASBMR).

Beyond diabetes remission a step further: Post bariatric surgery hypoglycemia.

Postbariatric hypoglycemia is a rare but increasingly recognized complication of bariatric surgery, with significant associated morbidity, and many patients often require multimodal treatment. A mixed meal challenge test is often helpful to diagnose this condition. This manuscript highlights the underlying mechanisms that lead to this condition and the novel emerging therapeutic targets that target these mechanisms.

Utility and validation of bone mineral density measurements at forearm in predicting trabecular microarchitecture and central-site osteoporosis in aging Indian postmenopausal women-a promising surrogate?

Objective: The objective of this paper was to present the results of our study of the utility of bone mineral density (BMD) measurements at various segments of distal forearm in predicting central-site osteoporosis and deteriorated trabecular microarchitecture. Methods: This was a cross-sectional study and BMD at the femoral neck, lumbar spine, and distal forearm were assessed using the dual-energy X-ray absorptiometry (DXA) scanner and bone microarchitecture at lumbar spine by trabecular bone score (TBS). The utility of forearm BMD in predicting osteoporosis as well as the deteriorated TBS was assessed by a receiver operating characteristic analysis. Results: A total of 352 postmenopausal women with mean (SD) age of 60.7 (6.8) years were included. The odds of having osteoporosis at femoral neck [odds ratio (OR) = 14.1, 95% confidence interval (CI): 7.8-25.2] and lumbar spine (OR = 7.5, 95% CI: 4.6-12.1) was highest with the mid-distal radius. A derived T-score cut off ≤ -1.6, -1.9, and -1.7 at any segment of the forearm was elucidated to predict osteoporosis at the central-site, femoral neck, and lumbar spine, respectively, with sensitivity of 80%-88% and specificity of 60%-70%. The T-scores at all three forearm segments ≤ -1.2 showed fair performance in predicting degraded trabecular microarchitecture. The T-scores thus derived were further validated in cohort of 360 Bengali postmenopausal women. Conclusion: BMD assessment at the forearm may be utilized in prediction of trabecular microarchitecture and central site osteoporosis at the femoral neck and lumbar spine in postmenopausal women.

Does hip structural analysis confer additional benefit to routine BMD assessment in postmenopausal women with hip fracture? A study from a tertiary center in southern India.

This study from southern India showed that proximal hip geometry was significantly impaired in postmenopausal women with femoral neck fracture. The trabecular bone score (TBS), which is reflective of bone microarchitecture, was also significantly impaired in patients with fracture. INTRODUCTION: There is limited information with regard to comprehensive bone health in Indian postmenopausal women with neck of femur fracture. We studied the bone mineral density (BMD), trabecular bone score (TBS), proximal hip geometry, and bone mineral biochemistry in postmenopausal women with and without femoral neck fractures. METHODS: This was a cross-sectional study conducted at a tertiary care center in South India. BMD, TBS, and hip structural analysis (HSA) were assessed using a dual-energy X-ray absorptiometry (DXA) scanner. Bone mineral biochemical profiles were also studied. RESULTS: A total of 90 postmenopausal women with acute femoral neck fracture with mean (SD) age of 63.2 (6.1) years and 90 age-matched controls were included. The prevalence of osteoporosis was higher among cases as compared to controls (83.3% vs 47.8%; P < 0.001). Degraded bone microarchitecture (TBS value < 1.200) was more frequent among women with hip fracture as compared to controls (46.7% vs 31.1%; P = 0.032). Cross-sectional moment of inertia (CSMI) was significantly lower at the narrow neck (NN) and inter-trochanteric (IT) region in cases (P < 0.05) and buckling ratio (BR) was significantly higher at all three sites in postmenopausal women with femoral neck fracture as compared controls. Multivariate logistic regression analysis showed that femoral neck osteoporosis, low CSMI at NN and high BR at NN and femoral shaft emerged as factors significantly associated with femoral neck fractures. CONCLUSION: This study highlights that impaired parameters of proximal hip geometry and a low trabecular bone score may be significantly associated with femoral neck fractures in postmenopausal women.

Prevalence and factors contributing to primary sarcopenia in relatively healthy older Indians attending the outpatient department in a tertiary care hospital: A cross-sectional study.

BACKGROUND: Literature is scarce on primary sarcopenia among Indian older adults. This study was aimed to estimate the prevalence of primary sarcopenia among older persons in India using the European Working Group on Sarcopenia in the Older People 2010 (EWGSOP) diagnostic criteria and to elucidate the factors leading to its development. METHODOLOGY: Two hundred twenty-seven subjects over 60 years of age attending the geriatric outpatient clinic were recruited for the study. Sarcopenia was diagnosed based on set criteria for gait speed, handgrip, and skeletal muscle mass assessment by dual-energy x-ray absorptiometry. RESULT: The prevalence of primary sarcopenia in the study population was 39.2% (n = 89). Male patients were more sarcopenic than women, 47% (n = 72) vs 23% (n = 17). Obese subjects (body mass index > 25 kg/m2) had a lower prevalence of sarcopenia (odds ratio = 0.10; 95% confidence interval = 0.05-0.19). There was no association between sarcopenia and other postulated risk factors like low vitamin D levels, dietary protein or carbohydrate intake, or sedentary lifestyle. CONCLUSION: Contrary to published data, primary sarcopenia appears to be higher among older Indians using presently available guidelines. Community studies with validated cutoffs suited for the Indian subcontinent may yield a lower prevalence of primary sarcopenia.

Persistent Idiopathic Prolactin Elevation Merits Macroprolactin Estimation: A Case Report and Review of Literature.

The prevalence of hyperprolactinemia ranges from about 0.4% in an unselected adult population to as high as 9%-17% in women with reproductive disorders. It may cause infertility in about 11% of the oligospermic males. Rarely, the cause of persistently elevated prolactin remains obscure even after thorough work up. Macroprolactinemia is biologically inactive, high-molecular-weight form of prolactin resulting from its binding to immunoglobulin G, causing a decrease in its clearance. We report the case of a 35-year-old female, detected to have hyperprolactinemia on multiple tests, during routine work up for primary infertility. Secondary causes for the same were ruled out. A magnetic resonance imaging (MRI) of the brain excluded a prolactinoma. This prompted an estimation of prolactin levels after polyethylene glycol precipitation which showed a decrease to 5.58 ng/mL, with <40% recovery, confirming the presence of macroprolactin. Thus, persistently elevated prolactin levels in the background of negative neurological imaging necessitate the estimation of macroprolactin.

Myelofibrosis and Pancytopenia Associated With Primary Hyperparathyroidism.

OBJECTIVE: Primary hyperparathyroidism (PHPT) has varied clinical presentations. Hematologic abnormalities secondary to PHPT have been described before. However, pancytopenia as the initial presentation has rarely been reported. We report a patient with PHPT who presented for evaluation of pancytopenia. METHODS: Histopathology of the bone marrow at presentation is described. Bone biochemistry results and the hematologic profile before and after curative parathyroidectomy are presented. RESULTS: A 48-year-old woman presented with pancytopenia (hemoglobin, 6.3 g/dL; total leucocyte count, 3000 cells/mm3; and platelet count, 60 000 cells/mm3), and her bone marrow study showed marrow fibrosis. Biochemical evaluation revealed hypercalcemia (15.5 mg/dL), hypophosphatemia (2.2 mg/dL), and elevated total alkaline phosphatase (4132 U/L). Bone mineral density assessment by dual-energy X-ray absorptiometry scan revealed osteoporosis at all 3 sites, which was more severe in the distal one third of the forearm. Further investigations confirmed the diagnosis of PHPT (serum parathyroid hormone, 2082 pg/mL). Following curative parathyroidectomy, in addition to normalization of calcium, there was restoration of all 3 hematologic cell lines at 3 months. CONCLUSION: Pancytopenia may be a rare manifestation of PHPT. Thus, it may be prudent to evaluate the calcium profile in patients with chronic refractory anemia and pancytopenia.

Clinical Profile and Mutations Associated with Multiple Endocrine Neoplasia-Type1 (MEN1) and Their First-Degree Relatives at Risk of Developing MEN1: A Prospective Study.

Multiple Endocrine Neoplasia type-1 (MEN1) is an autosomal dominant disorder with a combined occurrence of tumours of parathyroid glands, pancreatic islets, and anterior pituitary. About 90% of these patients carry mutations in the MEN1 gene, though the spectrum is not well defined in India. Forty clinically suspected cases of MEN1 were enrolled prospectively over six years; 32 patients (23 index-cases and nine affected relatives) with≥2 classical endocrine tumours of MEN1 were considered definite, and eight were categorised as 'MEN1-like'. Details of their clinical presentation, treatment and mutational analysis including MEN1 gene, 3' and 5' untranslated regions (UTR) of MEN1, CDKN1B, and CaSR genes were collated. Asymptomatic first-degree relatives were also screened. Among the 32 definite MEN1 patients, all had primary hyperparathyroidism, 22 (68.7%) had gastroentero-pancreatic neuroendocrine tumours, and 21 (66%) had pituitary adenoma. Of the 23 definite index-cases, 13 (56.5%) carried mutations in the MEN1 gene. Five of nine affected first-degree relatives (55.5%), and four of 10 asymptomatic relatives (40%) also had MEN1 mutations. Seven of 10 MEN1 mutation-negative definite index-cases harboured p.V109G polymorphism in the CDKN1B gene. All eight MEN1-like cases were negative for mutations and large deletions in MEN1, mutations in 3' and 5' UTR of MEN1, CaSR and CDKN1B genes. The study has helped to clearly document the pattern of mutations among Indian MEN1 patients. However, the absence of MEN1 mutation in ~44% of cases and the presence of p.V109G polymorphism in CDKN1B gene raise the question whether such polymorphisms could independently contribute to pathogenesis.

Dual-Energy X-Ray Absorptiometry Scanning in Practice, Technical Aspects, and Precision Testing.

The last three decades have witnessed considerable progress in the field of bone densitometry. Osteoporosis may be diagnosed in postmenopausal women and in men aged 50 and older if the bone mineral density (BMD) T-scores of the lumbar spine, total hip, or femoral neck are -2.5 or less. For reporting T-scores, the Hologic dual-energy X-ray absorptiometry (DXA) scanner uses the Caucasian (nonrace adjusted) female normative database for women and men of all ethnic groups although reference database used does have an impact on the categorization of BMD and must be chosen judiciously considering the regional and ethnic characteristics of the population. The quality control for DXA systems should be periodically done in accordance with manufacturer guidelines for DXA. Beyond conventional BMD assessment, DXA may also be utilized to assess the trabecular bone score, hip structural analysis, vertebral fractures, and body composition.

Screening Tools for Osteoporosis in India: Where Do We Place Them in Current Clinical Care?

The prevalence of osteoporosis is about 40%-50% in postmenopausal women and 20% in older men. The limited availability of dual-energy X-ray absorptiometry (DXA) scanners across the country calls for the presence of alternate risk assessment tools to identify those at high risk for osteoporosis. Some of the screening tools available for osteoporosis include Simple Calculated Osteoporosis Risk Estimation and Osteoporosis Risk Assessment Tool for Asians (OSTA), and Fracture Risk Assessment Tool to assess fracture risk. Clinical parameters that may serve as surrogates include dentition and anthropometric indices. Although screening tools do not supplant the assessment of bone mineral density by DXA, they help identify individuals at high risk for osteoporosis who may be selectively referred for confirming the same.

DXA Measured Visceral Adipose Tissue, Total Fat, Anthropometric Indices and its Association With Cardiometabolic Risk Factors in Mother-Daughter Pairs From India.

Visceral fat is the pathogenic fat depot associated with diabetes, dyslipidemia, and cardiovascular diseases. Estimation of visceral adipose tissue (VAT) by dual energy-X-ray absorptiometry (DXA) is a newer technique with less radiation exposure, shorter scanning time, and lower cost. In this study, we attempted to look at relationship between cardiometabolic risk factors and VAT, total body fat percent (TBF%) and anthropometry. We also studied the changes in body composition and metabolic parameters with menopause. The familial resemblance of VAT and TBF% in mother-daughter pair was also compared. This was a cross sectional community study of 300 women (150 postmenopausal mothers and 150 premenopausal daughters). Body composition indices by DXA and metabolic parameters were assessed. The association between DXA-VAT, TBF%, anthropometric measures, and cardiometabolic risk factors were studied by correlation, receiver operating characteristics curves, and logistic regression analysis. VAT indices were significantly higher and lean indices lower in postmenopausal women as compared to premenopausal women. One fourth of postmenopausal women were categorized as metabolically obese normal weight. DXA-VAT was a better predictor of cardiometabolic risk factors as compared to waist circumference, body mass index, and TF% in postmenopausal women (AUC:0.68 vs 0.62, 0.60 & 0.5, respectively), whereas body mass index had a better prediction in premenopausal women(AUC:0.68). VAT area >100 cm² had a significant association with the presence of ≥2 cardiometabolic risk factors (p = 0.04, OR: 2.2, CI:1.0-4.7) in the postmenopausal women. Daughters of the mothers with higher TBF% were found to have a higher TBF% compared to daughters of mothers with normal TBF% (36.2 ± 4.2 vs 32.2 ± 4.4, p = 0.03), similar resemblance was not seen for VAT. The study showed that the VAT increases and lean mass decreases with age and menopause. DXA measured VAT is a better predictor of cardiometabolic risk in postmenopausal women but not in premenopausal women. Total body fat may have a familial resemblance, but not the VAT which is determined by age, menopause, and probable life style factors.

A case of H. pylori infection presenting as refractory hypothyroidism.

We present the case of a 45-year-old lady with long standing hypothyroidism who was euthyroid on replacement for many years, but stopped responding even to supraphysiological doses of LT4 since the last five years. She complained of abdominal discomfort, bloating, and nausea. She did not have diarrhea or weight loss. Levothyroxine absorption test was done which was suggestive of malabsorption and she was started on triple therapy for H. pylori eradication after confirmation of diagnosis. After 10 days of treatment initiation, she developed symptoms of thyrotoxicosis with her supraphysiological dose of LT4, which was then tapered to a lower dose. Euthyroid state was ultimately achieved with lower doses of LT4 replacement.