Role of bisphosphonates in hypertrophic osteoarthropathy: a systematic review.

BACKGROUND: The role of bisphosphonates (BP) in hypertrophic osteoarthropathy (HPOA) is unclear. We presented a case of primary HPOA and performed a systematic review of literature on the effect of BP on treatment response in primary and secondary HPOA. METHODS: The study was prospectively registered in PROSPERO (CRD42022343786). We performed a PubMed literature search that restricted to the English language. We included patients diagnosed with primary or secondary HPOA who received BP. The primary endpoint assessed was the effectiveness of BP on response to pain or arthritis. Secondary outcomes included timing, degree, and duration of response, comparison to other HPOA therapies, impact of BP on radiology, bone scan, bone turnover markers, and adverse effects of BP. RESULTS: Literature search retrieved only case reports. Forty-five patients (21 primary, 24 secondary HPOA) had received BP. Majority(88.3%) experienced improvement in pain or arthritis. Response was gradual for primary HPOA and within a median of 3 to 7 days for secondary HPOA after treatment with BP. Most patients had reduced bone scan uptake after BP. When other HPOA therapies were tried, half responded to BP after not having previously responded to other therapies, while a third received the treatments concurrently, making it difficult to attribute treatment response to a drug. Reporting of other secondary outcomes was very heterogenous and qualitative to draw conclusions. No major adverse effects have been reported for BP in HPOA. CONCLUSION: Bisphosphonates provide an effective and safe treatment option for primary and secondary HPOA. However, there is a lack of randomized controlled trials.

Dyslipidaemia in endocrine disorders.

Lipid disorders are common in several endocrine conditions. Diabetes mellitus, hypothyroidism and Cushing's syndrome are the common endocrine disorders with dyslipidemia. Dyslipidemia has a significant impact on endocrine and metabolic health and the risk of atherosclerotic cardiovascular disease. In most cases of dyslipidemia, the suspicion of endocrine diseases must be based on clinical symptoms and signs. Optimal management of the dyslipidemia requires treatment of the underlying endocrine condition. Lipid lowering therapy is a useful adjunct or a requirement in many cases. The Indian guidelines provide a pragmatic and practical approach to the management of lipid disorders in endocrine disease, as well as endocrine vigilance with lipid therapy.

Do Bone Mineral Density, Trabecular Bone Score, and Hip Structural Analysis Differ in Indian Men with Parkinson's Disease? A Case-Control Pilot Study from a Tertiary Center in Southern India.

Objective: Parkinson's disease (PD) is a neurodegenerative condition that is characterized by bradykinesia, rigidity, and gait instability. Inherent to this condition is an increased predisposition to falls and fractures. Bone health in Parkinson's disease in India has not been studied thus far. This study aimed to assess the bone mineral density (BMD), trabecular bone score (TBS), and hip structural analysis (HSA) in Indian men with PD and compare them with matched controls. Methodology: A case-control study done at a tertiary care center from southern India. Bone biochemistry, BMD, TBS, and HSA were assessed. Results: Among 40 cases and 40 age, gender, and body mass index (BMI)-matched controls, there was no significant difference in BMD between both groups. The mean (SD) TBS at the lumbar spine [1.349 (0.090)] was significantly (P = 0.019) lower in men with PD as compared to matched controls [1.401 (0.089)]. Among the parameters of HSA, the buckling ratios were significantly higher at the femoral neck [11.8 (2.2) vs 9.4 (2.2); P = 0.001] and inter-trochanteric region [9.4 (2.1) vs 7.8 (1.4); P = 0.002] among cases as compared to matched controls. Vitamin D deficiency was significantly higher in this cohort of patients as was bone turnover marker indicating bone loss and a high bone turnover state. Conclusion: A comprehensive bone health assessment comprising BMD, TBS, and HSA may be required to capture all aspects of bone strength in Indian men with PD as BMD assessment as a stand-alone tool may not suffice to obtain all information pertaining to fracture risk in these individuals.

Growth hormone and gastrointestinal malignancy: An intriguing link.

Growth hormone (GH) excess is associated with several systemic complications, one of which is the increased risk of neoplastic processes particularly of the gastrointestinal (GI) tract. Among the GI neoplasms, the most reported association is with benign and malignant neoplasms of the colon. In the majority of published literature, an increased incidence of GI neoplasms, both colonic adenomas as well as colorectal carcinoma is reported. However, the studies on colon cancer-specific mortality rate are conflicting with recent studies reporting similar cancer-specific mortality rates in comparison to controls. Many studies have reported an association of colorectal neoplasms with GH levels. Pathogenic mechanisms put forward to explain this association of GH excess and GI neoplasms primarily involve the increased GH-insulin-like growth factor 1 (IGF-1) signaling. Both GH and IGF-1 have proliferative, anti-apoptotic, and angiogenic effects on the systemic tissues leading to cellular proliferation. Other contributing factors to the increased risk of GI neoplasms include slow intestinal transit with a redundant large bowel, altered bile acids, deranged local immune response, shared genetic susceptibility factors and hyperinsulinemia. In view of the increased risk association, most guidelines for the care of acromegaly patients recommend an initial screening colonoscopy. Recommendations for further follow-up colonoscopy differ but broadly, the guidelines agree that it depends on the findings at first colonoscopy and state of remission of GH excess. Regarding the concern about the risk of colorectal cancers in patients receiving recombinant GH therapy, most cohort studies do not show an increased risk.

Central hypothyroidism with myxoedema: a less known but clinically challenging presentation.

Myxoedema can have a variety of presentations, from mild cognitive impairment to psychosis, to overt coma. While majority of cases have primary hypothyroidism as the underlying aetiology, very few cases have central hypothyroidism. We report two patients who presented with myxoedema and were diagnosed with central hypothyroidism. A man in his 50s with a history of panhypopituitarism presented with hypotension, slurring of speech and psychosis that worsened to coma. He was initially treated as adrenal crisis, and on failing to improve he was later treated correctly as myxoedema coma. A woman in her 30s presented with bradykinesia and shock and was diagnosed with Sheehan's syndrome based on hormonal and imaging features. Both patients improved with a loading dose of oral thyroxine and intravenous steroids. Central hypothyroidism presenting with myxoedema is often complicated by coexisting pituitary hormone deficiencies. A high index of suspicion is required for better treatment outcomes.

Hypercalcaemia as the initial presentation of Graves' disease.

Hypercalcaemia in patients with hyperthyroidism is usually asymptomatic. It occurs due to increased bone turnover and demineralisation. There are only a few case reports where symptomatic hypercalcaemia was the presenting complaint of hyperthyroidism. An Asian man in his 40s presented to us with intractable vomiting for the last 6 months which was not controlled despite multiple antiemetic medications. On routine biochemistry performed at our institute, he was found to have hypercalcaemia and concomitant hyperthyroidism. Classical symptoms suggestive of hyperthyroidism were not present in our patient thus delaying the diagnosis. His symptoms resolved after the correction of hypercalcaemia. Hypercalcaemia did not recur after achieving an euthyroid status on treatment with carbimazole. Other common and more sinister causes for hypercalcaemia like malignancy were ruled out. This case highlights that symptomatic hypercalcaemia could be the initial presentation of hyperthyroidism and amelioration of hyperthyroidism corrects the hypercalcaemia.

Body composition and metabolic parameters in men with chronic traumatic paraplegia - A pilot study from India.

OBJECTIVE: To study body composition, measures of insulin resistance and dyslipidemia in Indian men with paraplegia as compared to age and body mass index (BMI) matched able-bodied men. DESIGN: Cross sectional study. SETTING: Departments of Physical Medicine and Rehabilitation and Endocrinology. PARTICIPANTS: Males aged 18-45 years with chronic traumatic paraplegia versus age and BMI-matched able-bodied men. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Measures of body composition such as total body fat, lean mass, regional adiposity using dual energy x-ray absorptiometry (DXA), metabolic profile and insulin resistance. RESULTS: Subjects with paraplegia (n = 43), compared to controls (n = 36), had higher %Fat mass (FM) (25.5 (21.2-28.9) vs 20.2 (15.9-22.2); P < 0.01), lower trunk to leg ratio (0.66 (0.51-0.73) vs 0.87 (0.72-0.94); P < 0.01), lower lean mass index (14.38 (2.57) vs 17.80 (2.34); P < 0.01) and lower appendicular lean mass index (5.81 ± 1.26 vs 8.17 ± 1.12; P < 0.01). Fasting blood glucose (mg/dl) was higher (89.0(81.5-96.5) vs 80.0 (74.5-88.2); P < 0.01), Homeostasis model assessment of insulin resistance was higher (1.33 (1.03-2.12) vs 0.94 (0.52-1.78); P = 0.02), Quantitative insulin sensitivity check index (QUICKI) was lower (0.36 ± 0.04 vs 0.38 ± 0.05; P = 0.02) and HDL-C was lower (33.00 (30.00-42.75) vs 38.50 (33.00-43.25); P < 0.02) in cases compared to controls. QUICKI correlated positively with HDL-C and negatively with %FM, estimated VAT volume and TG. Trunk to leg ratio correlated positively with TG even after controlling for %FM. CONCLUSION: Men with chronic paraplegia had lower lean mass, higher total and regional fat mass, increased insulin resistance and low HDL-C when compared with BMI-matched able-bodied controls. Both total and regional adiposity correlated with poor metabolic profile.

Diagnosis and treatment outcomes of Cushing's disease during pregnancy.

PURPOSE: We report a case of a pregnant woman with Cushing's disease (CD) and performed a systematic review of literature on diagnosis, treatment, maternal and fetal outcomes of CD in pregnancy. METHODS: A PubMed search was performed for manuscripts in English language from inception till June 2020. Cases of CD with hypercortisolism during pregnancy were included and categorized into three groups based on treatment received. Data on diagnostic modalities, CD remission, materno-fetal outcomes were analysed. RESULTS: Fifty-five patients of CD with 62 pregnancies were analysed. 24-h urinary free cortisol(UFC) was elevated by a mean of 5.4 ± 4.2 fold upper limit of normal non-pregnant level. 12/19 (63.1%) CD patients had more than threefold elevation of UFC measured during pregnancy. Mean midnight serum cortisol was 753.7 ± 270.5 nmol/l. At a midnight serum cortisol cut off of 440 nmol/l, 15/16 patients were correctly identified as CD. 23.2% underwent trans-sphenoidal surgery (group 1), 16.1% received only medical treatment (group 2) while 60.7% received no treatment (group 3) during pregnancy. Remission rates for CD in groups 1 and 2 were 76.9% and 77.8%, respectively. Adverse maternal and fetal outcomes were seen in 53.9% and 59.3% of the patients, respectively and were not significantly different between groups, although, lesser live births and greater pregnancy losses were seen in group 3. CONCLUSION: Midnight serum cortisol had better sensitivity than UFC for diagnosing hypercortisolism due to CD during pregnancy. In general, CD should be treated during pregnancy in order to optimize maternal and fetal outcomes as a trend towards increased live births is seen in treated subjects.

Utility of anthropometric indicators in predicting osteoporosis in ambulant community dwelling rural postmenopausal women from southern India.

Osteoporosis is characterised by low bone mineral density (BMD) and is a significant public health problem in India. This cross-sectional study was done to assess the relationship between various anthropometric measures and BMD in 308 rural dwelling South Indian postmenopausal women. Anthropometric variables such as weight, body mass index (BMI), waist circumference (WC), hip circumference (HC) and neck circumference (NC) were measured. BMD was assessed by dual-energy X-ray absorptiometry (DXA) scan at the lumbar spine (LS) and femoral neck (NOF). The mean age ± SD of study participants was 60.7 ± 7.8 years. All anthropometric variables showed positive correlation with BMD at NOF and LS (P < 0.05). Weight showed the best correlation (r = 0.482 for NOF and 0.412 for LS; P < 0.001). On multivariate logistic regression, age and weight remained significant for predicting femoral neck osteoporosis while weight and WC were the best predictors for LS osteoporosis. These anthropometric measures may serve as surrogate markers for osteoporosis and thus be used to screen postmenopausal women for referral to a centre with fewer limited resources.

Change in insulin resistance, beta cell function, glucagon-like peptide-1 and calcitonin levels two weeks after bariatric surgery.

AIM OF THE STUDY: Bariatric surgery causes profound improvement in metabolic parameters by increasing plasma glucagon like peptide - 1 (GLP-1) level even few weeks after surgery. GLP-1 analogues can cause calcitonin secreting medullary thyroid carcinoma in animals. The studies relating to the mechanisms that underlie these changes are few. The objectives of the study were to measure the change in insulin resistance, beta cell function, GLP-1 and calcitonin levels before and 2 weeks after bariatric surgery. METHODS: Patients above 18 years of age who underwent either laparoscopic sleeve gastrectomy or Roux-en Y gastric bypass were recruited into the study. Measured indices were homeostatic model assessment 2 for insulin resistance (HOMA2-IR), an index for hepatic insulin resistance; Matsuda index, an index of whole body insulin sensitivity; and insulin secretion and sensitivity index (ISSI-2), a marker of beta cell secretion. RESULTS: Twenty eight patients completed the study. HOMA2-IR was lower (2.72 ±â€¯1.28 vs. 2.04 ±â€¯0.9; P = 0.001) and ISSI-2 was higher (0.80 (0.51-1.26) vs. 1.04 (0.56-1.38); P = 0.019) at 2 weeks after surgery compared to baseline. Matsuda index also improved after surgery but was not statistically significant (2.02 (1.1-2.94) vs. 2.84 (1.56-4.12); P = 0.078). Fasting GLP-1 and calcitonin levels did not change while both peak GLP-1, and area under curve for GLP-1 were higher after surgery. CONCLUSIONS: At 2 weeks following bariatric surgery, hepatic insulin resistance decreased while beta cell function improved due to increase in postprandial GLP-1 level without any change in fasting calcitonin levels.

Insulin Sensitivity and Beta-Cell Function in Graves' Disease and Their Changes with the Carbimazole-Induced Euthyroid State.

BACKGROUND AND OBJECTIVE: Thyroid hormones play an important role in intermediate metabolism, and abnormal glucose tolerance is often observed in patients with hyperthyroidism. Several pathogenic mechanisms have been proposed as contributors. However, there is no conclusive evidence in the existing literature regarding the predominant underlying pathophysiology. Our objective was to determine the changes in insulin resistance parameters and beta-cell function in patients with Graves' disease following restoration of a euthyroid state. METHODOLOGY: This was an observational study with a before-after study design. Forty-five treatment-naïve adults with Graves' diseases were included and 36 completed the study. An oral glucose tolerance test was performed at baseline and after 3 months of achieving a stable euthyroid state to assess glucose tolerance, insulin sensitivity, and beta-cell function. All patients were treated with antithyroid medication. The outcome measures studied were the Homeostasis Model Assessment-2 Insulin Resistance (HOMA2-IR), Matsuda index, and Insulin Secretion-Sensitivity Index (ISSI)-2. RESULTS: Two-thirds of the patients had abnormal glucose tolerance at baseline. Among those with abnormal glucose tolerance at baseline, 34.7% had persistent abnormality during follow-up. During follow-up, no significant change was noted in the indices of insulin resistance. Patients with abnormal glucose tolerance had a significantly lower ISSI-2 index at baseline and it improved after achieving a euthyroid state. CONCLUSIONS: Abnormal glucose tolerance is a significant metabolic consequence in patients with Graves' disease. Decreased beta-cell function was observed among those with abnormal glucose tolerance and it improved during follow-up. In a proportion of patients, abnormal glucose tolerance persisted after 3 months, emphasizing the need for continued follow-up.

Response to Zoledronic Acid in Patients with Active Paget's Disease of Bone: A Retrospective Study.

BACKGROUND: Traditionally, bisphosphonates are used to treat active Paget's disease of bone (PDB). Intravenous zoledronic acid (ZA) is the most effective treatment option leading to sustained remission. OBJECTIVE: The primary objective of this study was to analyze the effect of intravenous ZA in patients with active PDB in a tertiary care center of India. MATERIALS AND METHODS: Retrospective data of 13 patients with active PDB who received a single dose of 4 mg intravenous ZA at our institute from January 2011 to June 2017 were reviewed. Response to therapy was monitored clinically, biochemically by serum alkaline phosphatase (ALP), and scintigraphically by 99m-Technetium methylene diphosphonate bone scan. RESULTS: All of our patients reported relief of bone pain. The mean duration of follow-up in our study was 35.2 ± 16.8 months. Serum ALP levels reduced significantly from 1190.9 ± 666.1 IU/L (n = 13) at baseline to 200.5 ± 68.4 IU/L (n = 13) at 6 months (P < 0.001). ALP level at 1 year was 174 ± 33.6 IU/L (n = 12), which remained stable till 36 months at 176.5 ± 50 IU/L (n = 8). This indicates that remission achieved by 6 months post ZA is sustained for at least 3 years. Scintigraphic ratio reduced from 9.6 [interquartile range (IQR) 5.25-18.2] at baseline to 2.7 (IQR 1.20-4.05) at follow-up (P < 0.001). Similarly, scintigraphic index of involvement reduced from 9.9 (IQR 5.6-28.5) at baseline to 3 (IQR 2-4) at follow-up (P = 0.018). CONCLUSION: A 4 mg single dose of intravenous ZA results in clinical, biochemical, and scintigraphic response that is sustained for at least 3 years.

Role of bisphosphonates in the management of acute Charcot foot.

Diabetes mellitus is the most common cause of Charcot neuropathy affecting foot and ankle. Acute Charcot foot (CF) presents with a red and swollen foot in contrast to the painless deformed one of chronic CF. Enhanced osteoclastogenesis plays a central role in the pathogenesis of acute CF. Many studies have shown elevated levels of bone turnover markers in patients with acute CF confirming it. These findings have led clinicians to use anti-resorptive agents [bisphosphonates (BP), calcitonin, and denosumab] along with immobilization and offloading in acute CF patients. The maximum evidence among all anti-resorptive agents is available for BPs, although its quality is low. Pamidronate has been shown to reduce the markers of activity of CF like raised skin temperature, pain, edema, and bone turnover markers in the majority of studies. Intravenous BPs are known to cause acute phase reactions leading to flu-like illness following their first infusion, which can be ameliorated by oral acetaminophen. Alendronate is the only oral BP used in these patients. It needs to be taken on an empty stomach with a full glass of water to avoid esophagitis. The side-effects and contraindications to BPs should be kept in mind while treating acute CF patients with them.