Clinical aspects of SARS-CoV-2 infection and vitamin D : COVID-19 and the endocrine system: special issue for reviews in endocrine and metabolic disorders (Felipe Casaneuva, Editor in Chief) A. Giustina and JP Bilezikian, Guest Editors.

In December 2019, the first cases of severe acute respiratory syndrome due to a new coronavirus (SARS-Cov-2), later designated as Covid-19, were described in China. With rapid advance of the infection to several continents, in March 2020, WHO declared this to be a pandemic. In April 2020, the first papers suggesting a possible role of Vitamin D deficiency in the severity of this infection began to appear and dozens of articles evaluating a potential relationship of vitamin D with COVID have emerged subsequntly. This possibility was raised based on pre-existing evidence of the effects of Vitamin D on the immune system, and more specifically on acute respiratory viral infections. In addition, most Covid-19 victims belong to groups at risk for vitamin D deficiency such as the elderly, obese, chronically ill, and specific ethnic groups. Although with some contradictory reports exist, most observational and cohort studies find a relationship of low vitamin D status with greater Covid severity, others, including the few interventional studies available show inconsistent results. This paper aims to present the rapidly expanding literature to date regarding the clinical relevance of vitamin D in Covid-19 and, consequently, the reasonableness of avoiding its deficiency to keep the immune system able to respond in the best way to this acute viral infection. In the meantime, we wait for publication of several prospective randomized controlled studies that are underway, evaluating the effects of treatment with vitamin D or metabolites on the severity of Covid-19 outcomes.

Hyperparathyroidism.

Primary hyperparathyroidism is a common endocrine disorder of calcium metabolism characterised by hypercalcaemia and elevated or inappropriately normal concentrations of parathyroid hormone. Almost always, primary hyperparathyroidism is due to a benign overgrowth of parathyroid tissue either as a single gland (80% of cases) or as a multiple gland disorder (15-20% of cases). Primary hyperparathyroidism is generally discovered when asymptomatic but the disease always has the potential to become symptomatic, resulting in bone loss and kidney stones. In countries where biochemical screening tests are not common, symptomatic primary hyperparathyroidism tends to predominate. Another variant of primary hyperparathyroidism has been described in which the serum calcium concentration is within normal range but parathyroid hormone is elevated in the absence of any obvious cause. Primary hyperparathyroidism can be cured by removal of the parathyroid gland or glands but identification of patients who are best advised to have surgery requires consideration of the guidelines that are regularly updated. Recommendations for patients who do not undergo parathyroid surgery include monitoring of serum calcium concentrations and bone density.

Diagnostic Performance of 4D CT and Sestamibi SPECT/CT in Localizing Parathyroid Adenomas in Primary Hyperparathyroidism.

Background There currently is no consensus on the optimal localization procedure and imaging protocol for parathyroid adenoma. Parathyroid four-dimensional (4D) CT has emerged as a promising method for preoperative localization. Purpose To evaluate the diagnostic performance of parathyroid 4D CT and technetium 99m-sestamibi (hereafter, referred to as sestamibi) SPECT/CT in preoperative localization in patients with primary hyperparathyroidism. Materials and Methods This was a single-institution retrospective study of patients with primary hyperparathyroidism who underwent a combined imaging protocol of sestamibi SPECT/CT and 4D CT (noncontrast, contrast agent-enhanced, arterial, and delayed venous phases) acquired in a single setting from February 2013 to May 2016, with subsequent parathyroidectomy within 6 months. Reference standard for correct localization was on the basis of location denoted on operative reports, with pathologic confirmation of parathyroid adenoma or hyperplasia. By using a four-quadrant analysis, sensitivity, specificity, and area under the curve (AUC) for localization of the hyperfunctioning parathyroid gland or glands at sestamibi SPECT/CT and 4D CT were compared, per modality and in combination. Results Four hundred patients (319 women, 81 men; mean age, 61 years ± 14 [standard deviation]) were evaluated. Similar diagnostic performance was found in both combined 4D CT with sestamibi SPECT/CT and 4D CT alone (area under the curve [AUC], 0.88 [95% CI: 0.86, 0.90] and 0.87 [95% CI: 0.85, 0.90], respectively; P = .82). Both modalities outperformed sestamibi SPECT/CT (AUC, 0.78; 95% CI: 0.76, 0.81; P < .001). Four-dimensional CT showed higher sensitivity than did sestamibi SPECT/CT (sensitivity, 79.3% [414 of 522] vs 58.0% [303 of 522], respectively; P < .001). In a subset analysis, 4D CT had higher sensitivity than sestamibi SPECT/CT in patients with single-gland disease (sensitivity, 92.5% [297 of 321] vs 75.1% [241 of 321], respectively; P < .001) and with multigland disease (sensitivity, 58.2% [117 of 201] vs 30.8% [62 of 201], respectively; P < .001). Conclusion Four-dimensional CT provided superior preoperative localization compared with sestamibi SPECT/CT in patients with single and multigland disease. The combination of the two modalities did not improve diagnostic performance compared with four-dimensional CT alone. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Sinha and Oates in this issue.

High Rate of Occult Urolithiasis in Normocalcemic Primary Hyperparathyroidism.

INTRODUCTION: Normocalcemic primary hyperparathyroidism (NPHPT) is characterized by elevations in serum parathyroid hormone levels in the presence of normal serum calcium concentrations after exclusion of secondary hyperparathyroidism. We have previously demonstrated no differences in the prevalence of clinically active urolithiasis between NPHPT and hypercalcemic asymptomatic PHPT, and that it is significantly higher in postmenopausal osteoporotic women with NPHPT in comparison to women with normal serum PTH and calcium concentrations. Few studies have addressed the occurrence of silent or occult kidney stones in asymptomatic hypercalcemic PHPT, but no data are available for NPHPT. OBJECTIVE: To determine the presence of occult urolithiasis in NPHPT patients using routine abdominal ultrasonography. METHODS AND RESULTS: We studied 35 patients with NPHPT (mean age 63.2 ± 10.7 years, 96% women; serum PTH 116.5 ± 39.2 pg/mL, 25OHD 38.5 ± 6.82 ng/mL, total calcium 9.1 ± 0.56 mg/dL; albumin 4.02 ± 0.37 g/dL; BUN 34.35 ±10.23 mg/dL; p = 3.51 ± 0.60 mg/dL; estimated glomerular filtration rate 88.44 ± 32.45 mL/min/1.73 m2, and 24-h urinary calcium excretion 140.6 ± 94.3 mg/24 h). The criteria for the diagnosis of NPHPT were as follows: serum PTH above the reference range (11-65 pg/mL), normal albumin-corrected serum calcium concentrations, normal 24-h urinary calcium excretion, serum 25OHD above 30 ng/mL, estimated GFR (MDRD) above 60 mL/min/1.73 m2 (with the exclusion of medications such as thiazide diuretics, lithium, bisphosphonates, and denosumab), a history of clinical symptoms of urolithiasis, and a family history of kidney stones. Thirty-five patients were evaluated and 25 of them met the inclusion criteria. Five patients presented nephrolithiasis corresponding to 20% of the study population. There were no statistically significant differences in any of the clinical or laboratory variables studied between patients with or without urolithiasis, although mean serum PTH levels were higher in patients with stones (180.06 ± 126.48 vs. 100.72 ± 25.28 pg/mL, p = 0.1). The size of the stones ranged from 0.6 to 0.9 cm and all of the stones were located in the renal pelvis. CONCLUSION: We found a high prevalence of occult kidney stones in NPHPT patients, similar to what is observed in clinically manifested urolithiasis, in hypercalcemic PHPT.

Multiple severe vertebral fractures during the 3-month period following a missed dose of denosumab in a postmenopausal woman with osteoporosis previously treated with alendronate
.

Denosumab is a monoclonal antibody that decreases bone resorption and increases bone mass and strength in trabecular and cortical bone leading to a reduction in fracture in women and men. Its effects are reversed after discontinuation. Recently, there has been concern about the discontinuation of denosumab and the increased risk of multiple vertebral fractures that would be associated with rapid bone loss due to high bone turnover and consequent increase in markers of bone remodeling, far above the baseline values. Some case reports have demonstrated the occurrence of more than two fractures within a period of 8 - 16 months after the drug's discontinuation. A 56-year-old female presented with multiple vertebral fractures in a short period of time after denosumab withdrawal. She took alendronate for 12 years since the occurrence of a rib fracture (from the age of 30 to 42 years). After a long period with no medication (12 years), she was placed on denosumab. On the day she was due to take the fourth injection, she had sudden back pain, and magnetic resonance imaging (MRI) showed a grade II fracture at T9. She had simply forgot to take the scheduled dose of denosumab. Three months later, she presented with several episodes of severe back pain and loss of height and was diagnosed with multiple new severe vertebral fractures. This case illustrates an uncommon and severe bone disease following the inadvertent discontinuation of denosumab treatment.
.

Occult urolithiasis in asymptomatic primary hyperparathyroidism.

OBJECTIVE: Recent international guidelines suggest renal imaging to detect occult urolithiasis in all patients with asymptomatic primary hyperparathyroidism (PHPT), but data regarding their prevalence and associated risk factors are limited. We evaluated the prevalence and risk factors for occult urolithiasis. METHODS: Cross-sectional analysis of 96 asymptomatic PHPT patients from a university hospital in the United States with and without occult nephrolithiasis. RESULTS: Occult urolithiasis was identified in 21% of patients. Stone formers had 47% higher 24-hour urinary calcium excretion (p = 0.002). Although available in only a subset of patients (n = 28), activated vitamin D [1,25(OH)2D] was 29% higher (p = 0.02) in stone formers. There was no difference in demographics, BMI, calcium or vitamin D intake, other biochemistries, renal function, BMD, or fractures. Receiver operating characteristic curves indicated that urinary calcium excretion and 1,25(OH)2D had an area under the curve of 0.724 (p = 0.003) and 0.750 (p = 0.04), respectively. A urinary calcium threshold of >211mg/day provided a sensitivity of 84.2% and a specificity of 55.3% while a 1,25(OH)2D threshold of >91pg/mL provided a sensitivity and specificity of 62.5% and 90.0% respectively for the presence of stones. CONCLUSION: Occult urolithiasis is present in about one-fifth of patients with asymptomatic PHPT and is associated with higher urinary calcium and 1,25(OH)2D. Given that most patients will not have occult urolithiasis, targeted imaging in those most likely to have occult stones rather than screening all asymptomatic PHPT patients may be useful. The higher sensitivity of urinary calcium versus 1,25(OH)2D suggests screening those with higher urinary calcium may be an appropriate approach.

Metabarcoding expands knowledge on diversity and ecology of rare actinobacteria in the Brazilian Cerrado.

Rare and unknown actinobacteria from unexplored environments have the potential to produce new bioactive molecules. This study aimed to use 16 s rRNA metabarcoding to determine the composition of the actinobacterial community, particularly focusing on rare and undescribed species, in a nature reserve within the Brazilian Cerrado called Sete Cidades National Park. Since this is an inaccessible area without due legal authorization, it is understudied, and, therefore, its diversity and biotechnological potential are not yet fully understood, and it may harbor species with groundbreaking genetic potential. In total, 543 operational taxonomic units (OTUs) across 14 phyla were detected, with Actinobacteria (41.2%), Proteobacteria (26.5%), and Acidobacteria (14.3%) being the most abundant. Within Actinobacteria, 107 OTUs were found, primarily from the families Mycobacteriaceae, Pseudonocardiaceae, and Streptomycetaceae. Mycobacterium and Streptomyces were the predominant genera across all samples. Seventeen rare OTUs with relative abundance < 0.1% were identified, with 82.3% found in only one sample yet 25.5% detected in all units. Notable rare and transient genera included Salinibacterium, Nocardia, Actinomycetospora_01, Saccharopolyspora, Sporichthya, and Nonomuraea. The high diversity and distribution of Actinobacteria OTUs indicate the area's potential for discovering new rare species. Intensified prospection on underexplored environments and characterization of their actinobacterial diversity could lead to the discovery of new species capable of generating innovative natural products.

Hypopituitarism due to a Large Osteoclastoma Arising from the Sphenoid Bone Invading the Pituitary Fossa in a Patient with Parathyroid Carcinoma.

Background: Parathyroid carcinoma accounts for <1% of cases of primary hyperparathyroidism (PHPT). This rare condition may present with severe hypercalcemia and bone complications such as osteoclastomas and pathologic fractures. Here, we present a rare condition of panhypopituitarism resulting from an osteoclastoma in the sphenoid bone that invaded the pituitary fossa due to parathyroid carcinoma. Case Report. A 47-year-old woman previously diagnosed with PHPT underwent a parathyroidectomy 6 years earlier, with histological examination indicating a parathyroid adenoma. After surgery, she continued to exhibit high serum parathyroid hormone (PTH) and calcium levels, with the development of bone pain and spontaneous fractures. Imaging exams showed a large osteoclastoma of the sphenoid bone, invading the pituitary fossa, causing hypopituitarism. A new parathyroidectomy was performed, with histological confirmation of parathyroid carcinoma and regression of the osteoclastoma. Conclusion: This case illustrates an unusual presentation of parathyroid carcinoma, in which an osteoclastoma of the sphenoid bone caused hypopituitarism.

Anabolic therapy for osteoporosis: update on efficacy and safety.

Anabolic agents for the treatment of osteoporosis increase bone density, improve bone strength, and reduce fracture risk. They are distinguished from antiresorptive drugs by their property of increasing osteoblastic bone formation. Teriparatide and abaloparatide are parathyroid hormone receptor agonists that increase bone remodeling with bone formation increasing more than bone resorption. Romosozumab is a humanized monoclonal antibody to sclerostin that has a "dual effect" of increasing bone formation while decreasing bone resorption. The bone forming effects of anabolic therapy appear to be self-limited, making it imperative that it be followed by antiresorptive therapy to enhance or consolidate the beneficial effects achieved. Teriparatide, abaloparatide, and romosozumab each have unique pharmacological properties that must be appreciated when using them to treat patients at high risk for fracture. Clinical trials have shown a favorable balance of expected benefits and possible risks. Anabolic therapy is superior to bisphosphonates for high-risk patients, with greater benefit when initial treatment is with an anabolic agent followed by an antiresorptive drug, rather than the reverse sequence of therapy. Recent clinical practice guidelines have included recommendations with examples of patients who are candidates with anabolic therapy.

The Role of Bisphosphonates Prior to Denosumab Treatment on Rebound Fractures: A Mini Review.

Denosumab is a potent anti-resorptive medication used to treat patients at high risk for osteoporosis; however, its beneficial effects on the skeletal system are quickly reversed after discontinuation. In contrast, bisphosphonates (BPs) are anti-resorptive agents with residual effects on the bone matrix; thus, these are capable of preserving bone mass for a long time. Therefore, subsequent anti-resorptive treatment with BPs is mandatory to prevent rebound fractures. Furthermore, BP administration before denosumab treatment appears to be a reasonable strategy for reducing hyperactivation of bone remodeling. In this review, we summarize the effects of BP administration before denosumab treatment in preventing rebound fractures after denosumab discontinuation.

Male osteoporosis.

Osteoporosis, a disease classically attributed to postmenopausal women, is underappreciated, underdiagnosed, and undertreated in men. However, it is not uncommon for osteoporotic fractures to occur in men. About 40% of fractures occur in men with an incidence that has increased over the years. After a first fracture, the risk of a subsequent episode, as well as the risk of death, is higher in the male than in the female population. Despite these facts, only 10% of men with osteoporosis receive adequate treatment. Up to half of the cases of male osteoporosis have a secondary cause, the most common being hypogonadism, excessive alcohol consumption, and chronic use of glucocorticoids. The International Society for Clinical Densitometry (ISCD) recommends using the female database for the diagnosis of osteoporosis by DXA (T-score ≤ -2.5 in men over 50 years old). In addition, osteoporosis can also be diagnosed independently of the BMD if a fragility fracture is present, or if there is a high risk of fractures by FRAX. Treatment is similar to postmenopausal osteoporosis, because the data regarding changes in bone density track closely to those in women. Data concerning fracture risk reduction are not as certain because the clinical trials have included fewer subjects for shorter period of time. In men with symptomatic hypogonadism, testosterone replacement, if indicated, can improve BMD.

Occult Renal Calcifications in Patients with Normocalcemic Primary Hyperparathyroidism and Their Association with the Parathyroid Hormone-Vitamin D Axis.

Normocalcemic primary hyperparathyroidism (NPHPT) is characterized by elevated serum levels of parathyroid hormone (PTH) with persistently normal serum calcium concentrations after excluding secondary causes of hyperparathyroidism. Urolithiasis and/or nephrocalcinosis may occur in hypercalcemic PHPT, but little is known about these complications in NPHPT. Objectives. To identify occult urolithiasis and nephrocalcinosis in asymptomatic patients with NPHPT and evaluate biochemical markers as risk predictors for the development of renal calcification (RC). Methods. Cross-sectional analysis of 34 patients with no history of urolithiasis and/or nephrocalcinosis. The diagnosis of NPHPT was as follows: elevated serum PTH (reference range: 15-65 pg/mL), normal albumin-corrected serum calcium, normal urinary calcium excretion, serum 25(OH)D >30 ng/mL, eGFR (CKD-EPI) > 60 mL/min/1.73 m2, without intestinal disease, and not on medications such as thiazide diuretics, lithium, bisphosphonates, or denosumab. Patients were categorized according to the presence or absence of RC identified by renal imaging. Their clinical and biochemical characteristics were then compared. Results. The patients had a mean age of 67.97 ± 10.45 years, predominantly postmenopausal women (88.2%); serum PTH, 119.67 ± 64.44 pg/mL; 25(OH)D, 39.00 ± 8.88 ng/dL; 1.25(OH))2D, 74.53 ± 26.37 pg/mL; corrected serum calcium, 9.34 ± 0.62 mg/dL; and 24-hour urinary calcium, 134.87 ± 79.68 mg/day. RC was identified in 26.5% of the patients. There was no difference in anthropometric and clinical parameters, renal function, 25(OH)D, and urinary pH in patients with or without RC. Patients with RC had higher PTH values (176.22 vs. 99.32 pg/mL, P = 0.001), 1.25(OH) 2D (96.83 vs. 62.36 pg/mL, P = 0.005), and 24-hour urinary calcium (181.9 vs. 117.94 mg/day, P = 0.037). Conclusion. Occult renal calcifications are common in NPHPT and are associated with increased serum PTH, 1.25(OH))2D, and 24 h urinary calcium.

Impaired physical function and evaluation of quality of life in normocalcemic and hypercalcemic primary hyperparathyroidism.

INTRODUCTION: Severe primary hyperparathyroidism may be associated with muscle weakness and fatigue, but little is known about this effect in milder forms of the disease. This study aimed to evaluate physical function and quality of life in patients with normocalcemic (NPHPT) and hypercalcemic (HPHPT) primary hyperparathyroidism. METHODS: This was a case-control study on 40 postmenopausal women. Thirteen patients with NPHPT, 7 patients with HPHPT, and their controls were studied. Mean serum PTH in the control group was 49.10 ± 12.38 pg/mL. All of the participants answered the Medical Outcomes Short-Form Health Survey (SF36) and were submitted to 2 strength tests (Hand Grip strength and Chair stand test) and 2 performance tests for physical function (Short physical performance battery and Gait speed). Body composition analysis was performed by dual-energy X-ray absorptiometry (DXA) and multifrequency bioimpedance (BIA). RESULTS: Patients with NPHPT had lower grip strength (p = 0.005), a higher mean time of the chair stand test (p = 0.012), a lower mean gait speed (p < 0.001) and a lower score for the Short Physical Performance Battery (SPPB) (p = 0.010) than the control group. Patients with HPHPT had lower handgrip strength (p = 0.027), a higher mean time of the chair stand test (p = 0.017), and a lower score for the SPPB (p = 0.049) than the control group. Patients with NPHPT showed a higher gait speed when compared to HPHPT (p = 0.048). There was no difference between BIA and DXA body composition indices between the PHPT groups and their controls. The evaluation of the SF-36 showed significantly less quality of life in the general health domain among the NPHPT group and in the mental health domain among the HPHPT than in the controls. CONCLUSION: Patients with NPHPT and HPHPT have decreased physical performance and strength.

Vitamin D Deficiency, Skin Phototype, Sun Index, and Metabolic Risk Among Patients with High Rates of Sun Exposure Living in the Tropics.

Objective: We sought to evaluate serum 25-hydroxycholecalciferol (vitamin D [25-OHD]) levels, skin phototype, and sun index in a sample of patients to determine the association between these factors and metabolic risk. Design: This was a cross-sectional study involving 729 adults (50.2% male). Mean age was 65.13±9.18 years, sun index 5.71±5.06, body mass index (BMI) 27.60±5.34 kg/m2, and waist circumference 97.29±12.08cm. Hypertension, metabolic syndrome, and Type 2 diabetes were reported in 77.8, 74.5, and 38.9 percent, respectively; Fitzpatrick Skin Types III and IV were reported in 60.6 percent. Results: Mean serum 25-OHD was 25.72±10.91ng/mL; 31 percent of subjects had serum 25-OHD below 20ng/mL, and 63.1 percent had serum 25-OHD below 30ng/mL. Although there were no significant differences between the vitamin D deficient and sufficient groups regarding age, BMI, waist circumference, or presence of diabetes, in the group with 25-OHD less than 20ng/mL (sun index of 4.5±4.08), higher serum triglycerides and lower high-density lipoprotein cholesterol (HDL-C) levels were measured: triglycerides 179.14±103.53 versus 161.63±90.23mg/dL (p=0.029) and HDL-C 43.48±12.38 versus 45.94±14.14mg/dL (p=0.018) compared to the group with 25-OHD levels of 20ng/mL or higher (sun index: 6.25±5.36). Considering less than 25th percentile (25-OHD: 18.7ng/mL) and 75th percentile or higher (25-OHD: 30.8 ng/mL), the differences in serum triglycerides remained significant: 176.63±103.79 versus 157.47±80.49 (p=0.039). Conclusion: We found a high prevalence of vitamin D deficiency in individuals with high sun exposure, regardless of age, BMI, and waist circumference. This deficiency was associated with increased serum triglycerides and decreased HDL-C levels.

Robust Trabecular Microstructure in Type 2 Diabetes Revealed by Individual Trabecula Segmentation Analysis of HR-pQCT Images.

Type 2 diabetes (T2D) patients have an increased fracture risk, which may be partly explained by compromised bone microarchitecture within the cortical bone compartment. Data on trabecular bone parameters in T2D are contradictory. By high-resolution peripheral quantitative computed tomography (HR-pQCT), trabecular microarchitecture is preserved, yet larger trabecular holes are detected in T2D by MRI and DXA-based trabecular bone scores are abnormal. To determine if there are differences in trabecular microstructure, connectivity, and alignment in postmenopausal women with T2D as compared with controls, we performed an individual trabecula segmentation (ITS) analysis on HR-pQCT scans of the distal radius and tibia in 92 women with (n = 42) and without (n = 50) T2D. Unadjusted analyses showed that T2D subjects had greater total trabecular bone volume, trabecular plate volume fraction, plate number density, plate junction density, and axial alignment at the radius and tibia, and increased plate tissue fraction, but decreased rod tissue fraction and rod length at the radius (p < 0.05 for all). After adjustments for clinical covariates, plate number density and plate junction density remained higher at the radius and tibia, whereas total trabecular bone volume was increased and trabecular rod length was decreased at the radius. These differences remained significant after adjustment for hip BMD and trabecular volumetric bone density. Notably, the increased plate-like ITS qualities were seen in those with T2D duration of <10 years, whereas ITS parameters in subjects with T2D duration ≥10 years did not differ from those of control subjects. In conclusion, postmenopausal women with early T2D had a greater plate-like and less rod-like trabecular network. This early advantage in trabecular plate quality does not explain the well-established increased fracture risk in these patients and does not persist in the later stage of T2D. © 2018 American Society for Bone and Mineral Research.

Novel Therapies for Postmenopausal Osteoporosis.

Recently discovered mechanisms have assisted in developing new therapies for osteoporosis. New classes of drugs have been developed for the treatment of postmenopausal osteoporosis. Although there have been numerous advances over the past 2 decades, the search for newer therapies continues.

Anabolic therapy for osteoporosis: update on efficacy and safety

ABSTRACT Anabolic agents for the treatment of osteoporosis increase bone density, improve bone strength, and reduce fracture risk. They are distinguished from antiresorptive drugs by their property of increasing osteoblastic bone formation. Teriparatide and abaloparatide are parathyroid hormone receptor agonists that increase bone remodeling with bone formation increasing more than bone resorption. Romosozumab is a humanized monoclonal antibody to sclerostin that has a "dual effect" of increasing bone formation while decreasing bone resorption. The bone forming effects of anabolic therapy appear to be self-limited, making it imperative that it be followed by antiresorptive therapy to enhance or consolidate the beneficial effects achieved. Teriparatide, abaloparatide, and romosozumab each have unique pharmacological properties that must be appreciated when using them to treat patients at high risk for fracture. Clinical trials have shown a favorable balance of expected benefits and possible risks. Anabolic therapy is superior to bisphosphonates for high-risk patients, with greater benefit when initial treatment is with an anabolic agent followed by an antiresorptive drug, rather than the reverse sequence of therapy. Recent clinical practice guidelines have included recommendations with examples of patients who are candidates with anabolic therapy.

Romosozumab for the treatment of osteoporosis.

INTRODUCTION: Sclerostin, a glycoprotein produced primarily by osteocytes, blocks the canonical Wnt signaling bone formation pathway. Romosozumab is a humanized monoclonal antibody to sclerostin that binds to sclerostin, permitting the engagement of Wnt ligands with their co-receptors, resulting in an increase in bone formation and bone mineral density (BMD). Clinical studies with romosozumab have shown dramatic improvements in BMD at the spine and hip. Romosozumab is associated with improvement in bone strength through mechanisms that include increases in bone formation and, different from classical osteoanabolic agents, suppression of bone resorption. Areas covered: Herein, the authors highlight the available data on romosozumab for the treatment of osteoporosis. This includes the latest data on the efficacy, pharmacokinetics and pharmacodynamics as well as safety and tolerability data. Expert opinion: Monthly subcutaneous dosing of romosozumab reduces the risk of vertebral and clinical fractures in women with postmenopausal osteoporosis, with a favorable balance of benefits and risks. Romosozumab is a promising emerging anabolic agent with a novel mechanism of action that may expand the options for treating osteoporotic patients at high risk of fracture.

Male osteoporosis

ABSTRACT Osteoporosis, a disease classically attributed to postmenopausal women, is underappreciated, underdiagnosed, and undertreated in men. However, it is not uncommon for osteoporotic fractures to occur in men. About 40% of fractures occur in men with an incidence that has increased over the years. After a first fracture, the risk of a subsequent episode, as well as the risk of death, is higher in the male than in the female population. Despite these facts, only 10% of men with osteoporosis receive adequate treatment. Up to half of the cases of male osteoporosis have a secondary cause, the most common being hypogonadism, excessive alcohol consumption, and chronic use of glucocorticoids. The International Society for Clinical Densitometry (ISCD) recommends using the female database for the diagnosis of osteoporosis by DXA (T-score ≤ −2.5 in men over 50 years old). In addition, osteoporosis can also be diagnosed independently of the BMD if a fragility fracture is present, or if there is a high risk of fractures by FRAX. Treatment is similar to postmenopausal osteoporosis, because the data regarding changes in bone density track closely to those in women. Data concerning fracture risk reduction are not as certain because the clinical trials have included fewer subjects for shorter period of time. In men with symptomatic hypogonadism, testosterone replacement, if indicated, can improve BMD.

Thyroglobulin levels before radioactive iodine therapy and dynamic risk stratification after 1 year in patients with differentiated thyroid cancer.

OBJECTIVES: We sought to assess the relationship between stimulated thyroglobulin (sTg) before radioactive iodine therapy (RIT), and the dynamic risk stratification 1 year after treatment, and to establish the utility of the sTg as a predictor of response to therapy in these patients. A retrospective chart review of patients with differentiated thyroid cancer (DTC) who underwent RIT after surgery and were followed for at least 1 year, was carried out. SUBJECTS AND METHODS: Patients were classified according to the dynamic risk stratification 1 year after initial treatment. The sTg values before RIT were compared among the groups. ROC curve analysis was performed. RESULTS: Fifty-six patients were enrolled (mean age 44.7 ± 14.4 years, 80.7% had papillary carcinoma). Patients with excellent response had sTg = 2.1 ± 3.3 ng/mL, those with indeterminate response had sTg = 8.2 ± 9.2 ng/mL and those with incomplete response had sTg = 22.4 ± 28.3 ng/mL before RIT (p = 0.01). There was a difference in sTg between excellent and incomplete response groups (p = 0.009) while no difference was found between indeterminate and either excellent or incomplete groups. The ROC curve showed an area under the curve of 0.779 assuming a sTg value of 3.75 ng/mL. CONCLUSION: Our study results suggest that the higher the sTg before RIT, the greater the likelihood of an incomplete response to initial treatment. A sTg cut-off of 3.75 ng/mL was found to be a good predictor of response to initial treatment in patients with DTC.