Characterization of primary hyperparathyroidism based on target organ involvement: An analysis from the Indian PHPT registry.

BACKGROUND: It has been a matter of debate for long time about the existence of two distinct phenotypes of primary hyperparathyroidism (PHPT) predisposed to either renal or skeletal manifestation. OBJECTIVE: To differentiate characteristics of symptomatic PHPT patients based on the presence of skeletal or renal involvement. DESIGN: Retrospective analysis of data from the Indian PHPT registry. PATIENTS: PHPT patients were divided into four discrete groups: asymptomatic, presenting with renal manifestations alone, skeletal manifestations alone, and both skeletal and renal manifestations. MEASUREMENTS: Clinical, biochemical, and tumour weight and histopathological characteristics of these groups were compared. RESULTS: Of the 229 eligible patients, 45 were asymptomatic, 62 had renal manifestations, 55 had skeletal manifestations, and 67 had both skeletal and renal manifestations. Patients with both skeletal and renal manifestations had higher serum calcium levels than those with isolated skeletal involvement [12.5 (11.1-13.7) mg/dL, 11.2 (10.6-12.3) mg/dL, respectively; p < .05]. Serum alkaline phosphatase (AP), plasma parathyroid hormone (PTH) levels, and parathyroid tumour weight were significantly higher in patients with isolated skeletal, and both skeletal and renal manifestations, compared to the other two groups. A preoperative PTH and AP level of 300 pg/mL and 152 U/L, predicted the risk of developing skeletal involvement with sensitivity and specificity of 71%, 70%, and 69%, 67%, respectively. CONCLUSIONS: We observed distinct skeletal and renal phenotypic subgroups among PHPT patients with characteristic biochemical and hormonal patterns with higher parathyroid disease burden in patients with skeletal complications compared to those with isolated renal manifestation.

Baseline renal dysfunction determines mortality following parathyroidectomy in primary hyperparathyroidism: analysis of Indian PHPT registry.

INTRODUCTION: Primary hyperparathyroidism (PHPT) in India is mostly symptomatic with renal and skeletal complications. Evidence on mortality outcomes following parathyroidectomy from India, where the disease is predominantly symptomatic is limited. MATERIAL AND METHODS: This was a prospective study to evaluate mortality outcomes in the Indian PHPT registry over the past 25 years (n = 464). Pre- and postoperative parameters and mortality data were obtained from medical records and/or by verbal autopsy, a method validated by WHO for data collection in settings where several deaths are noninstitutional. Patients were divided into survivor (SG) and nonsurvivor groups (NSG) to ascertain differences in presentation and the effect of parathyroidectomy. RESULTS: The overall mortality was 8.8% at a median follow-up of 8 years (IQR 1-13) after parathyroidectomy. Chronic kidney disease was the most common background cause of death (43.5%), followed by pancreatitis (28.2%). NSG had significantly more frequent renal dysfunction (91.9% vs 73.9%), anaemia (50 vs 16.6%) and pancreatitis (24.3 vs 6.4%). PTH (61.9 vs 38.3 pmol/l) and baseline creatinine (97.2 vs 70.7 µmol/l) were significantly higher and eGFR lower (66.7 vs 90.7 ml/min/1.73m2) in the NSG than SG. By Cox proportional modelling, renal dysfunction [HR 2.88 (1.42-5.84)], anaemia [HR 2.45 (1.11-5.42)] and pancreatitis [HR 2.65 (1.24-5.66)] on univariate and renal dysfunction [HR 3.33 (1.13-9.77)] on multivariate analysis were significant for mortality. Survival curves demonstrated a significantly higher mortality with lower eGFR values. CONCLUSIONS: Nonsurvivors in PHPT had greater prevalence and more severe baseline renal dysfunction than survivors. Survival after parathyroidectomy was significantly associated with estimated glomerular filtration rate at baseline.

Patient Perspectives on the COVID-19 Vaccine: A Pilot Survey Study of Patients in Endocrinology Clinics.

OBJECTIVE: Vaccine hesitancy is an impediment to fighting the COVID-19 pandemic. Endocrinology clinics routinely see patients who are at high risk of a more aggressive form of COVID-19, including patients with diabetes, obesity, and hypertension. As patients with endocrine-related conditions often require multiple visits each year, endocrinology clinics provide a significant opportunity for vaccine education. The aim of our study was to evaluate patient perspectives about COVID-19 vaccination in outpatient endocrinology clinics. METHODS: A pilot survey study of patients who visited 3 endocrinology clinics between May 31, 2021, and June 18, 2021. A 7-item questionnaire explored the patients' perspectives and behaviors regarding COVID-19 vaccination. Data were analyzed with descriptive statistics. RESULTS: A total of 446 patients from 3 clinic locations (1 urban and 2 suburbans) completed our survey. There were 361 (81%) patients who indicated that they were planning to or had already received the COVID-19 vaccination, 56 (13%) reported no intent for vaccination, and 29 (7%) were unsure. Of the 85 patients who were unsure or did not intend to be vaccinated, 43 (51%) were Black, 30 (35%) were White, and 4 (5%) had other racial/ethnic identities. When asked about vaccine hesitancy, 25 (29%) wanted to wait and see how the others responded to the vaccine, 20 (24%) had concerns about the side effects, 12 (14%) did not believe in vaccines, and 11 (13%) felt that COVID-19 was not as bad as the media had portrayed it. Significantly more Black patients had vaccine hesitancy than White patients (P = .035). CONCLUSION: Although most endocrinology patients were amenable to COVID-19 vaccination, a subpopulation still expressed vaccine hesitancy, indicating that endocrinology clinics may be an ideal place for targeted vaccine education.

Role of Phosphate in Biomineralization.

Inorganic phosphate is a vital constituent of cells and cell membranes, body fluids, and hard tissues. It is a major intracellular divalent anion, participates in many genetic, energy and intermediary metabolic pathways, and is important for bone health. Although we usually think of phosphate mostly in terms of its level in the serum, it is needed for many biological and structural functions of the body. Availability of adequate calcium and inorganic phosphate in the right proportions at the right place is essential for proper acquisition, biomineralization, and maintenance of mass and strength of the skeleton. The three specialized mineralized tissues, bones, teeth, and ossicles, differ from all other tissues in the human body because of their unique ability to mineralize, and the degree and process of mineralization in these tissues also differ to suit the specific functions: locomotion, chewing, and hearing, respectively. Biomineralization is a dynamic, complex, and lifelong process by which precipitations of inorganic calcium and inorganic phosphate divalent ions form biological hard tissues. Understanding the biomineralization process is important for the management of diseases caused by both defective and abnormal mineralization. Hypophosphatemia results in mineralization defects and osteomalacia, and hyperphosphatemia is implicated in abnormal excess calcification and/or ossification, but the exact mechanisms underlying these processes are not fully understood. In this review, we summarize available evidence on the role of phosphate in biomineralization. Other manuscripts in this issue of the journal deal with other relevant aspects of phosphate homeostasis, phosphate signaling and sensing, and disorders resulting from hypo- and hyperphosphatemic states.

Effect of serum 25-hydroxyvitamin D concentrations on skeletal mineralization in black and white women.

INTRODUCTION: There is controversy over the adverse effect of vitamin D deficiency on bone mineralization. The purpose of this study was to determine the ethnical differences in vitamin D and bone mineralization as well as the association between vitamin D deficiency and bone mineralization defects. MATERIALS AND METHODS: We examined serum 25-hydroxyvitamin D (25(OH)D) levels and transiliac bone biopsies in 92 healthy black and white women, aged 20-73 years. The major bone mineralization indices include osteoid volume per bone volume (OV/BV), osteoid surfaces per bone surface (OS/BS), osteoid thickness (O.Th) and mineralization lag time (Mlt). RESULTS: 25(OH)D levels were significantly lower and prevalence of 25(OH)D deficiency was significantly higher in blacks than in whites. However, none of the mineralization indices showed significant difference between the two groups. In addition, there was no significant correlation between 25(OH)D levels and mineralization indices in both black and white cohorts. Only one case had O.Th marginally greater than 12.5 µm, which is the cutoff value for identifying bone mineralization defects. OV/BV and OS/BS, but not O.Th, were significantly positively correlated with activation frequency (Ac.f). CONCLUSIONS: Our study indicated: (1) vitamin D deficiency is common, but bone mineralization is not impaired in black women, and (2) there are no significant correlations between serum 25(OH)D levels and bone mineralization indices, suggesting that vitamin D deficiency may not be an independent factor contributing to bone mineralization defects and osteomalacia.

Progressive rise in the prevalence of asymptomatic primary hyperparathyroidism in India: Data from PHPT registry.

INTRODUCTION: Primary hyperparathyroidism (PHPT), a third common endocrine disorder, varies from asymptomatic disease, mostly seen in the West where routine biochemical screening is practiced, to the classical symptomatic disease mostly seen in the Eastern countries. We aimed to compare the demographic, clinical, biochemical measurements in patients with asymptomatic and symptomatic PHPT from the Indian PHPT registry. MATERIAL AND METHODS: Data of PHPT patients from the last 25 years (1995-2019) were analyzed for demographic, clinical presentation and biochemical measurements, and compared these characteristics between asymptomatic and symptomatic PHPT patients. RESULTS: Of the 554 patients, 54 (10%) patients had asymptomatic PHPT. There was a sharp rise in the proportion of asymptomatic PHPT patients of 3% in the first decade to 13% in the second decade of the century (p = 0.003). Patients with asymptomatic PHPT were significantly older (50 vs. 42 years; p < 0.0001) and had higher mean body mass index (27.8 vs. 23.5 kg/m2; p < 0.0001) compared to the symptomatic PHPT group. In addition, asymptomatic PHPT patients had significantly lower median plasma iPTH (180 vs. 370 pg/mL; p < 0.0001), serum alkaline phosphatase (119 vs. 172 IU/L; p < 0.0001), and parathyroid adenoma weight (1.0 vs. 2.62 g; p = 0.006) compared to the symptomatic PHPT group. CONCLUSION: Although symptomatic PHPT is still most prevalent (> 90%) in India with higher indices of the disease and tumor weights, there is a progressive rise in the prevalence of asymptomatic PHPT patients in the last decade. Improvements in calcium and vitamin D nutrition might account for this change as in the Western series.

Differences in Primary Hyperparathyroidism Between Pre- and Postmenopausal Women in India.

OBJECTIVE: Primary hyperparathyroidism (PHPT) is a common endocrine disorder in women which becomes more prevalent after menopause. In this study, we compared the demographic, clinical, and biochemical variables between premenopausal (pre-M) and postmenopausal (post-M) women with PHPT. METHODS: A retrospective analysis (from 2005 to 2019) of enrolled women PHPT patients from an online Indian PHPT registry. RESULTS: Of the women with PHPT, 232 and 122 were pre-M and post-M, respectively. The number of post-M PHPT cases registered had a 3.3-fold increase in 2015-2019 from 2005-2009 compared with only a 2.5-fold increase in pre-M cases in the same duration. The majority were symptomatic (90%), although pre-M had a higher proportion of symptomatic than post-M (92% vs 85%; P = .04). Pre-M women showed more prevalence of osteitis fibrosa cystica than post-M women (28% vs 13%; P = .03), although hypertension and gallstone disease were seen more frequently in post-M PHPT women. Pre-M women had a significantly higher median PTH (403 vs 246 pg/mL; P = .02) and median alkaline phosphatase (202 vs 145 pg/mL; P = .02) than post-M women, and vitamin D deficiency was more common in pre-M women (58% vs 45%; P = .03). Gland localization, tumor weight, and disease cure rates did not differ according to menopausal status. CONCLUSION: PHPT was more prevalent in pre-M women, although the number of post-M cases had significantly increased in the last 10 years. Pre-M women had generally more severe clinical and biochemical variables than post-M PHPT women.

Reference Intervals for Bone Histomorphometric Measurements Based on Data from Healthy Premenopausal Women.

This study has established the normal reference intervals for bone histomorphometric measurements derived from healthy premenopausal women, which is rarely available. We presented the static and dynamic bone histomorphometric data from trans-iliac bone biopsies in 62 healthy premenopausal women (19 blacks and 43 whites, ages 20-53 years). There were no significant differences in age and BMI between black and white women. Since there was no significant difference in bone remodeling between the two ethnic groups, we pooled data of all 62 premenopausal women to establish normal reference intervals for bone histomorphometry. The results provide normal reference intervals for both static and dynamic histomorphometric variables in cancellous and cortical bone of the ilium. None of the bone remodeling-related variables correlated with age or BMI. This study provides reference intervals for bone histomorphometric measurements in both cancellous and cortical bone of the ilium, which would be helpful in the evaluation of bone health in women.

UTILITY OF AFIRMA GENE EXPRESSION CLASSIFIER FOR EVALUATION OF INDETERMINATE THYROID NODULES AND CORRELATION WITH ULTRASOUND RISK ASSESSMENT: SINGLE INSTITUTIONAL EXPERIENCE.

Objective: We assessed our experience with Afirma gene expression classifier (GEC) combined with sono-graphic risk assessment, using both the American Thyroid Association (ATA) and the Thyroid Imaging Reporting and Data System (TI-RADS) in evaluating indeterminate thyroid nodules. Methods: We identified 98 patients with 101 nodules who had a second fine needle aspiration biopsy (FNA) between January 1, 2014, and September 30, 2017, and sent to Veracyte for cytopathology and subsequent Afirma GEC testing. A second FNA biopsy was performed if the initial cytopathology was either Bethesda III or IV (n = 94) or nondiagnostic (n = 7). We correlated cytopathology, histopathology, and Afirma GEC results with sonographic risk assessment using both the ATA system and TI-RADS. Results: The mean age of the cohort was 57.4 ± 12.3 years; 84% women and 60% white. Repeat FNA was benign in 51 of 101 nodules, and of the remaining 50 nodules, 18 (36%) were GEC-benign and 32 (64%) GEC-suspicious. Eighteen of the 32 GEC-suspicious nodules underwent surgery with the following results: 7 benign (39%), 1 follicular thyroid carcinoma (6%), 6 follicular variant of papillary thyroid cancer (33%), and 4 noninvasive follicular tumor with papillary-like nuclear features (22%). The malignancy rate among the surgical cohort was 39% (without noninvasive follicular tumor with papillary-like nuclear features [NIFTP]) and 61% (with NIFTP) and about 50% and 20% of this group scored in the high suspicion category by ATA and TR5 by TI-RADS, respectively. Conclusion: Afirma GEC was useful in avoiding surgery in one-third of indeterminate nodules and performed similarly to ATA and TI-RADS. However, the use of echogenicity in scoring may underestimate the risk of malignancy in patients with indeterminate nodules. Abbreviations: ATA = American Thyroid Association; AUS = Atypia of Undetermined Significance; FLUS = Follicular Lesion of Undetermined Significance; FN = follicular neoplasm; FNA = fine needle aspiration; FTC = follicular thyroid cancer; FVPTC = follicular variant of papillary thyroid cancer; GEC = Gene Expression Classifier; ND = nondiagnostic; NIFTP = noninvasive follicular tumor with papillary-like nuclear features; TI-RADS = Thyroid Imaging Reporting and Data System; TR = TI-RADS.

The Hyperechoic Appearance of the Deltoid Muscle on Shoulder Ultrasound Imaging as a Predictor of Diabetes and Prediabetes.

OBJECTIVES: To evaluate whether the ultrasound appearance of the deltoid muscle in diabetic patients differs from that in obese nondiabetic patients. METHODS: Ultrasound images of the deltoid muscle from 137 type 2 diabetic patients (including 13 prediabetic patients) and 49 obese nondiabetic patients were blindly reviewed by 2 musculoskeletal radiologists, and by a third when arbitration was needed, to determine whether the appearance was "normal," "suspected diabetes," or "definite diabetes." Age, sex, race, body mass index (BMI), insulin use, and hemoglobin A1c were analyzed. This retrospective study included patients presenting between October 2005 and November 2017. Statistical analyses included a 2-sided sample t test or Wilcoxon rank sum test and a χ2 or Fisher exact test. Statistical significance was defined as P < .05. RESULTS: The type 2 diabetic patients included 98 women and 39 men aged 29 to 92 years, and the nondiabetic patients included 19 women and 30 men aged 18 to 75 years. A consensus diagnosis of definite diabetes by the musculoskeletal radiologists based on a hyperechoic deltoid was a powerful predictor of diabetes, with a positive predictive value of 89%. A hyperechoic deltoid was also a powerful predictor of prediabetes. Of the 13 prediabetic patients, all had the same hyperechoic appearance of the diabetic deltoid, regardless of BMI. Although obese diabetic patients more often had a diagnosis of definite diabetes, the BMI alone could not explain the increased echogenicity, as obese nondiabetic patients' deltoid muscles did not appear as hyperechoic and were correctly categorized as not having definite diabetes with 82% specificity. CONCLUSIONS: The characteristic hyperechoic deltoid appearance is a strong predictor of both diabetes and prediabetes and differs from that of obese nondiabetic patients.

Fibrogenesis Imperfecta Ossium.

Fibrogenesis imperfecta ossium (FIO) is an extremely uncommon fatal bone disorder of poorly understood etiology. The pathogenesis of FIO is not well known. The fundamental skeletal defect appears to be an abnormality in organic matrix of bone characterized by defective mineralization of the abnormal collagen. FIO clinically manifests in middle-aged adults presenting with fracture and bone pain. Elevated serum alkaline phosphatase is the only and the most consistent biochemical abnormality. Although paraproteinemia is observed in one-third of cases, the pathogenic link to the disease process is unclear. Limited information on FIO and its close resemblance to many metabolic bone disorders leads to delayed or missed diagnoses and management. Prednisolone, bisphosphonates, melphalan and steroids have been tried previously with variable success. Recently, a trial of recombinant growth hormone therapy was found to be effective. Further research focused on the pathogenetic mechanisms of FIO is needed to identify and develop targeted therapeutic options.

Pituitary Dysfunction Among Men Presenting with Hypogonadism.

PURPOSE OF REVIEW: Hypogonadism is a common endocrine dysfunction. This review focuses on the most up-to-date guideline for evaluation of pituitary function among men presenting with signs and symptoms of hypogonadism. RECENT FINDINGS: The clinician must differentiate between primary (testicular) and secondary (pituitary-hypothalamic or central) hypogonadisms and be aware of adult-onset hypogonadism. If gonadotropins are low or inappropriately normal, the clinician must consider potential reversible causes in the hypothalamus-pituitary axis. Also, it is critical to understand the pitfalls of testosterone testing. When clinically indicated, evaluation of other pituitary hormone functions as well as pituitary magnetic resonance imaging may be necessary. Furthermore, it is essential to recognize that pituitary incidentalomas are common. Patients with microprolactinoma are more likely to present with symptoms of sexual dysfunction while those with macroprolactinoma are more likely to present with symptoms of mass effect. Some functional pituitary tumors respond to drug therapy while other nonfunctional tumors require surgical intervention. It is important for the clinician to understand the proper work-up of the hypogonadal patient with pituitary dysfunction and when necessary to refer to an endocrinologist or a neurosurgeon.

Trueness, precision and stability of the LIAISON 1-84 parathyroid hormone (PTH) third-generation assay: comparison to existing intact PTH assays.

BACKGROUND: Over the past few decades, parathyroid hormone (PTH) immunoassays have progressed through successive generations resulting in increased specificity and accuracy for detecting circulating PTH. With the introduction of third-generation assays, in which the biologically active PTH(1-84) is specifically targeted, the PTH(7-84) and other fragments are not detected. The specific recognition of only PTH(1-84) whole molecule allows for more reliable standardization and calibration than with the existing assays. METHODS: Samples from patients on hemodialysis or with primary hyperparathyroidism and apparently healthy subjects were examined in different collection matrices (EDTA plasma, unspun EDTA plasma and SST) stored for 0, 24 or 72 h at room temperature to reflect the prevailing sample collection methods, shipping and processing conditions of centralized labs in the United States. Samples were analyzed by the LIAISON 1-84 PTH and N-TACT assays, and by three additional commercially available intact PTH assays. RESULTS: Defined samples, prepared using two different standards (WHO 95/646 international standard and the synthetic Bachem PTH(1-84)), show little bias with the LIAISON 1-84 PTH assay, but not with the other intact PTH assays. Furthermore, PTH is stable for up to 72 h in plasma, but less stable in serum beyond 24 h. CONCLUSIONS: The FDA-approved LIAISON 1-84 PTH assay is accurate and reliably measures the biologically active PTH molecule in plasma or serum stored at room temperature for up 72 and 24 h, respectively.

Bone Structure and Turnover Status in Postmenopausal Women with Atypical Femur Fracture After Prolonged Bisphosphonate Therapy.

Atypical femur fracture (AFF), a serious complication of long-term bisphosphonate therapy, is usually preceded by an incomplete fracture appearing on the lateral femur. AFF is most likely the result of severely suppressed bone turnover (SSBT). However, the differences in bone structure and turnover between patients with incomplete and complete AFF remain unknown. We examined trans-iliac bone biopsies from 12 white postmenopausal women with AFF (incomplete = 5; complete = 7) on BP therapy of >5 years and 43 healthy white premenopausal women. Histomorphometric measurements were performed separately in cancellous, intracortical and endosteal envelopes. Of the 43 histomorphometric measurements on 3 difference bone surfaces (cancellous, intracortical and endosteal), only 2 bone resorption variables (Oc.S/BS and Oc.S/NOS) on the endosteal surface were significantly lower in patients with complete AFF than those with incomplete AFF. Compared to healthy premenopausal women, the trabecular bone volume, thickness and number were all significantly lower in patients with AFF. The dynamic bone formation variables in patients with AFF were significantly reduced on all bone surfaces. The likelihood of a biopsy with no tetracycline labeling was significantly higher in AFF patients than in healthy premenopausal women. Based on these results, we conclude that there are no significant differences in bone turnover between patients with incomplete and complete AFF, suggesting that the suppression of bone turnover had already existed in the femur with incomplete AFF. Compared to healthy premenopausal women, bone turnover is similarly suppressed in patients with either type of AFF.

PREVALENCE AND PREDICTORS OF PRIMARY HYPERPARATHYROIDISM AMONG PATIENTS WITH UROLITHIASIS.

OBJECTIVE: Urolithiasis may be the only presenting manifestation of primary hyperparathyroidism (PHPT), and early detection of PHPT in such patients may prevent future urolithiasis and other PHPT complications. This study was performed to study the prevalence and predictors of PHPT in patients presenting with urolithiasis. METHODS: Consecutive patients presenting with urolithiasis were evaluated for clinical and biochemical manifestations of PHPT with serum and urine calcium (Ca), serum intact parathyroid hormone and 25 (OH) vitamin D. We then compared the clinical and biochemical characteristics of PHPT patients presenting with urolithiasis (group A) and without (group B). RESULTS: During the 3-year study period, 381 patients with urolithiasis were seen with a mean age of 38.5 ± 13.9 years. Nineteen of the 381 (5%) patients had histologically proven PHPT (group A). Four patients in group A (21%) and 8 in group B (2%) had nephrocalcinosis (P<.0001), multiple stones (≥3), calcific pancreatitis, and neuropsychiatric manifestations were more common in group A (P<.0001). Presence of multiple or bilateral stones, and recurrent stone episodes predicted PHPT (odds ratio [OR]: 3.06, confidence interval [CI]: 0.87, 0.7). CONCLUSION: One out of every 20 patients with urolithiasis had PHPT, which is higher than the prevalence of PHPT in general population. The presence of nephrocalcinosis and multiple, bilateral, and recurrent stone disease increased the risk of PHPT among stone formers. ABBREVIATIONS: Ca = calcium; CI = confidence interval; iPTH = intact parathyroid hormone; nPHPT = normocalcemic PHPT; OR = odds ratio; PHPT = primary hyperparathyroidism.

ANABOLIC BONE WINDOW WITH WEEKLY TERIPARATIDE THERAPY IN POSTMENOPAUSAL OSTEOPOROSIS: A PILOT STUDY.

OBJECTIVE: Osteoporosis is a major public health problem that reduces bone strength and increases fracture risk. Teriparatide is an established and the only currently available anabolic therapy for the treatment of postmenopausal osteoporosis (PMO) with a recommended daily dose of 20 µg given subcutaneously. However, there are limited data regarding the long-term effect of once-weekly teriparatide therapy on bone mineral density (BMD), bone turnover markers (BTMs), and anabolic bone window. METHODS: In this prospective observational study, 26 patients with PMO were treated with weekly teriparatide therapy (60 µg) for 2 years. BMD was measured at baseline, 12 months, and 24 months. The bone formation marker type 1 collagen C-terminal propeptide (P1NP) and the bone resorption marker C-terminal telopeptide of type 1 collagen (CTx) were measured at baseline; 6 weeks; and 6, 12, 18, and 24 months. RESULTS: BMDs at the lumbar spine increased by 3.1% and 10.8% after 1 and 2 years of weekly teriparatide therapy, respectively. The T-score increased significantly at the lumbar spine compared to baseline after 2 years of therapy (P = .015). Serum P1NP levels increased significantly at 6 months (P = .024), peaked at 1 year, and remained above the baseline even after 2 years. Serum CTx levels decreased significantly at 6 months (P = .025) and remained below baseline after 2 years of teriparatide therapy. CONCLUSION: Weekly teriparatide therapy (60 µg) appears to be as effective as daily teriparatide for the treatment of PMO by extending the anabolic bone window. ABBREVIATIONS: AE = adverse event; BMD = bone mineral density; BTM = bone turnover marker; CTx = C-terminal telopeptide of type 1 collagen; DXA = dual-energy X-ray absorptiometry; iPTH = intact parathyroid hormone; P1NP = type 1 collagen C-terminal propeptide; PMO = postmenopausal osteoporosis.

The advantages of tomosynthesis for evaluating bisphosphonate-related atypical femur fractures compared to radiography.

OBJECTIVE: To investigate the advantages of using tomosynthesis (TS) compared to radiographs in the detection, characterization, and follow-up of bisphosphonate-related atypical femur fractures (BP-AFF). SUBJECTS AND METHODS: Eight patients were identified retrospectively who underwent TS for radiographic findings suspicious for BP-AFF. Two radiologists independently interpreted 15 radiographs and 16 TS examinations, indicating the presence or absence of the following: (1) cortical "beaking" on radiographs, (2) radiolucent fracture line on radiographs, and (3) fracture lucency on TS corresponding to the site of radiographic abnormality. Radiation dose data were calculated for radiographs and TS using Monte Carlo analysis. RESULTS: There was agreement on 100 % of radiographs regarding the presence or absence of a cortical beak. Regarding the presence or absence of a fracture lucency, there was agreement on 100 % of TS examinations (Kappa = 1.0) and 73 % of radiographs (Kappa = 0.40 ± 0.24). For the 46 % of radiographs in which one or both radiologists did not visualize a fracture line, there was 100 % agreement for the presence of a fracture line on the corresponding TS. The interobserver agreement for fracture line detection was significantly higher for TS than for radiographs (p = 0.012). The effective radiation dose using TS was approximately 96 % lower compared to radiography. CONCLUSION: TS outperformed radiographs in the detection and characterization of BP-AFF. TS may also have advantages over radiography for BP-AFF follow-up through its unique ability to visualize fracture healing with lower effective radiation doses to the patient.

Changes in parathyroid proteome in patients with primary hyperparathyroidism due to sporadic parathyroid adenomas.

PURPOSE: The pathogenesis of parathyroid tumours is only partially understood. A direct approach using proteomics could be a promising tool to increase our understanding of parathyroid tumorigenesis. The aim of the study was to investigate differentially expressed proteins to explore the underlying molecular basis of the disease and identify potential target proteins responsible for the genesis of adenoma. METHODS: Proteins were extracted from adenomatous and normal parathyroid tissues. Differentially expressed proteins were separated by two-dimensional gel electrophoresis (2-D) and identified by matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry. Statistical analysis was performed using spss 10.01 software. RESULTS: Comparative analysis of the 2-D profiles of proteins isolated from adenomatous and normal parathyroid tissues showed 15 differentially expressed proteins, of which 11 were overexpressed. The characterized proteins were associated with diverse cellular functions including regulation of cell organization, programmed cell death, transcription and signal transduction. CONCLUSION: The differentially expressed proteins in parathyroid adenomas may potentially serve as new targets to investigate the mechanisms of parathyroid adenoma transformation.

Differences in bone histomorphometry between White postmenopausal women with and without atypical femoral fracture after long-term bisphosphonate therapy.

Bone histomorphometric endpoints in transilial biopsies may be associated with an increased risk of atypical femoral fracture (AFF) in patients with osteoporosis who take antiresorptives, including bisphosphonates (BPs). One way to test this hypothesis is to evaluate bone histomorphometric endpoints in age-, gender-, and treatment time-matched patients who either had AFF or did not have AFF. In this study, we performed transiliac bone biopsies in 52 White postmenopausal women with (n = 20) and without (n = 32) AFFs, all of whom had been treated for osteoporosis continuously with alendronate for 4-17 yr. Despite the matched range of treatment duration (4-17 yr), AFF patients received alendronate for significantly longer time (10.7 yr) than non-AFF patients (8.0 yr) (P = .014). Bone histomorphometric endpoints reflecting microstructure and turnover were assessed in cancellous, intracortical, and endocortical envelopes from transilial biopsy specimens obtained from BP-treated patients 3-6 mo after AFF and from non-AFF patients with similar age-, gender-, and range of BP treatment duration. However, in both cancellous and intracortical envelopes, AFF patients had significantly lower wall thickness (W.Th) and higher osteoclast surface (Oc.S/BS) than non-AFF patients. In addition, AFF patients had significantly higher eroded surface (ES/BS) only in the intracortical envelope. None of the dynamic variables related to bone formation and turnover differed significantly between the groups. In conclusion, in the ilium of BP-treated patients with osteoporosis, AFF patients have lower thickness of superficial bone (lower W.Th) of the cancellous and cortical envelopes than non-AFF patients. AFF and non-AFF patients have a similar bone turnover rate in the ilium. Furthermore, in this population, as in previous work, AFF is more likely to occur in BP-treated patients with longer treatment duration.

Bisphosphonates (BPs) are widely used to prevent osteoporotic fracture and treat osteoporosis. However, prolonged use of BPs may increase the risk of atypical femoral fracture (AFF), and their pathogenesis remains unclear. This study compared the bone histomorphometric findings in cancellous and cortical bones between White osteoporotic women with (n = 20) and without AFF (n = 32), who had received BP treatment for a matched duration of 4­17 yr. The BP-treated patients with AFF had significantly lower wall thickness (W.Th) in both cancellous and cortical bones compared to BP-treated patients without AFF. There were no significant differences in bone formation, turnover, or mineral apposition rate between BP-treated AFF and non-AFF patients. In conclusion, our study results suggest that AFF risk is increased in BP-treated patients with smaller young and healthy superficial bone areas (indicated by lower W.Th). Surprisingly, we also discovered that patients with and without AFF have similar bone turnover rates, which contradicts previous beliefs. Our findings provide valuable insights into the potential factors contributing to AFF in BP-treated patients.

Vitamin D for the Prevention of Disease: An Endocrine Society Clinical Practice Guideline.

BACKGROUND: Numerous studies demonstrate associations between serum concentrations of 25-hydroxyvitamin D (25[OH]D) and a variety of common disorders, including musculoskeletal, metabolic, cardiovascular, malignant, autoimmune, and infectious diseases. Although a causal link between serum 25(OH)D concentrations and many disorders has not been clearly established, these associations have led to widespread supplementation with vitamin D and increased laboratory testing for 25(OH)D in the general population. The benefit-risk ratio of this increase in vitamin D use is not clear, and the optimal vitamin D intake and the role of testing for 25(OH)D for disease prevention remain uncertain. OBJECTIVE: To develop clinical guidelines for the use of vitamin D (cholecalciferol [vitamin D3] or ergocalciferol [vitamin D2]) to lower the risk of disease in individuals without established indications for vitamin D treatment or 25(OH)D testing. METHODS: A multidisciplinary panel of clinical experts, along with experts in guideline methodology and systematic literature review, identified and prioritized 14 clinically relevant questions related to the use of vitamin D and 25(OH)D testing to lower the risk of disease. The panel prioritized randomized placebo-controlled trials in general populations (without an established indication for vitamin D treatment or 25[OH]D testing), evaluating the effects of empiric vitamin D administration throughout the lifespan, as well as in select conditions (pregnancy and prediabetes). The panel defined "empiric supplementation" as vitamin D intake that (a) exceeds the Dietary Reference Intakes (DRI) and (b) is implemented without testing for 25(OH)D. Systematic reviews queried electronic databases for publications related to these 14 clinical questions. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology was used to assess the certainty of evidence and guide recommendations. The approach incorporated perspectives from a patient representative and considered patient values, costs and resources required, acceptability and feasibility, and impact on health equity of the proposed recommendations. The process to develop this clinical guideline did not use a risk assessment framework and was not designed to replace current DRI for vitamin D. RESULTS: The panel suggests empiric vitamin D supplementation for children and adolescents aged 1 to 18 years to prevent nutritional rickets and because of its potential to lower the risk of respiratory tract infections; for those aged 75 years and older because of its potential to lower the risk of mortality; for those who are pregnant because of its potential to lower the risk of preeclampsia, intra-uterine mortality, preterm birth, small-for-gestational-age birth, and neonatal mortality; and for those with high-risk prediabetes because of its potential to reduce progression to diabetes. Because the vitamin D doses in the included clinical trials varied considerably and many trial participants were allowed to continue their own vitamin D-containing supplements, the optimal doses for empiric vitamin D supplementation remain unclear for the populations considered. For nonpregnant people older than 50 years for whom vitamin D is indicated, the panel suggests supplementation via daily administration of vitamin D, rather than intermittent use of high doses. The panel suggests against empiric vitamin D supplementation above the current DRI to lower the risk of disease in healthy adults younger than 75 years. No clinical trial evidence was found to support routine screening for 25(OH)D in the general population, nor in those with obesity or dark complexion, and there was no clear evidence defining the optimal target level of 25(OH)D required for disease prevention in the populations considered; thus, the panel suggests against routine 25(OH)D testing in all populations considered. The panel judged that, in most situations, empiric vitamin D supplementation is inexpensive, feasible, acceptable to both healthy individuals and health care professionals, and has no negative effect on health equity. CONCLUSION: The panel suggests empiric vitamin D for those aged 1 to 18 years and adults over 75 years of age, those who are pregnant, and those with high-risk prediabetes. Due to the scarcity of natural food sources rich in vitamin D, empiric supplementation can be achieved through a combination of fortified foods and supplements that contain vitamin D. Based on the absence of supportive clinical trial evidence, the panel suggests against routine 25(OH)D testing in the absence of established indications. These recommendations are not meant to replace the current DRIs for vitamin D, nor do they apply to people with established indications for vitamin D treatment or 25(OH)D testing. Further research is needed to determine optimal 25(OH)D levels for specific health benefits.