Metabolic syndrome and central fat distribution are related to lower serum osteocalcin concentrations.

BACKGROUND: The aim of this study was to evaluate the association of serum osteocalcin with the metabolic syndrome (MS) in men and premenopausal women. METHODS: 14 middle-aged men and 44 premenopausal women were evaluated. MS was defined according to the International Diabetes Federation criteria. Anthropometric data were collected and serum osteocalcin, serum C-telopeptide (CTX), fasting plasma glucose (FPG) and lipid profile measured. RESULTS: The mean age was 41.07 ± 8.4 years and did not differ between patients with and without MS. Mean osteocalcin was significantly lower in patients with MS (11.18 ± 4.62 vs. 15.09 ± 5.05, p = 0.003) and decreased significantly with the rise in the number of criteria for diagnosis of MS. There were no significant differences in serum CTX between the two groups. Serum osteocalcin was lower in patients with body mass index (BMI) ≥25 (p = 0.038) and FPG ≥100 mg/dl (p = 0.024), and in hypertensive (p = 0.013) and diabetic patients (p = 0.036), and was inversely associated with BMI (p = 0.024), waist circumference (WC) (p = 0.024), FPG (p = 0.007) and systolic blood pressure (SBP) (p = 0.037). CONCLUSION: This study showed that lower serum osteocalcin is associated with the presence of MS and that osteocalcin is inversely associated with BMI, WC, FPG and SBP, suggesting that osteocalcin plays a part in the development of MS.

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.

Characteristics of Paget's disease of bone in the city of Recife, Brazil.

In South America the incidence of Paget's disease of bone (PDB) is low and more than half of the cases published in the last 30 years come from Brazil and Argentina. The aim of this study was to describe the clinical and epidemiological characteristics of PDB in two institutions in Pernambuco. PDB patients in Recife, Brazil were studied retrospectively. A total of 108 cases were diagnosed from 1984 to 2005. Over 90% of the patients were of European descent. The average age was 66.2 years and 49.1% were male. The polyostotic form was the more common. Pain and bone deformity were significantly more frequent in this group and in the total group. Clear eyes were observed in 22.2% of the patients and 23.1% had a family history record of PDB. The most frequently affected bones were the pelvis, lumbar vertebrae, femurs, and skull. Zoledronate was the most effective drug in reducing the alkaline phosphatase. Our data show that PDB in Recife occurs predominantly among those of European descents, usually in the polyostotic presentation, thus providing evidence of genetic and historical factors in the prevalence of PDB in that region.

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.

Prevalence of cortical osteoporosis in mild and severe primary hyperparathyroidism and its relationship with bone markers and vitamin D status.

Studies on the prevalence of site-specific osteoporosis in patients with different clinical presentations of primary hyperparathyroidism (PHPT) are scarce in the literature. The present study aims to determine the prevalence of cortical osteoporosis in such patients by using 3-site dual-energy X-ray absorptiometry (lumbar spine, femoral neck, 1/3 radius). We studied 49 patients, 12 males and 37 females, with PHPT, who were separated into 3 groups: asymptomatic (AS), renal stone disease (RS), and osteitis fibrosa cystica (OF). Osteoporosis occurred as follows: lumbar spine-48% for AS, 17.6% for RS, and 100% for OF (p=0.0004); femoral neck-20% for AS, 12% for RS, and 85.7% for OF (p=0.0014); 1/3 radius-71% for AS, 53% for RS, and 86% for OF (p=0.2845). Serum calcium, parathyroid hormone, alkaline phosphatase, and beta-carboxy-terminal telopeptide were significantly higher in the OF group. The mean values for 25-hydroxyvitamin D were lower in OF group than AS and RS groups (15.2+/-6.3 ng/mL vs. 22.7+/-11.9 ng/mL and 20.3+/-7.0 ng/mL; p=0.2139). Based on these results, we conclude that the prevalence of osteoporosis is high in all sites studied and is almost universal in the OF patients. The great prevalence of cortical osteoporosis is seen even in young patients with less severe forms of the disease.

Differences in accuracy of 99mTc-sestamibi scanning between severe and mild forms of primary hyperparathyroidism.

UNLABELLED: Preoperative localization of the parathyroids using (99m)Tc-sestamibi scanning has not yet been established as a routine diagnostic procedure for primary hyperparathyroidism. Several studies have demonstrated a variable degree of accuracy (70%-98%) in asymptomatic patients. METHODS: We evaluated the accuracy of this technique in 64 patients who underwent scanning between January 2000 and January 2005 according to the clinical manifestations of the disease. RESULTS: The study included 25 asymptomatic patients (group I), 18 nephrolithiasis patients without overt bone disease (group II), and 21 patients with severe bone involvement and osteitis fibrosa cystica (group III). Mean serum calcium in groups I, II, and III was 10.98 +/- 0.02, 11.32 +/- 0.17, and 13.35 +/- 0.35 mg/dL, respectively. Mean serum parathyroid hormone in groups I, II, and III was 135.45 +/- 13.50, 165.85 +/- 15.06, and 579.6 +/- 628.4 pg/mL, respectively. The (99m)Tc-sestamibi scan results were positive in 64% of the patients in group I, in 83% of those in group II, and in 100% of those in group III. Of the patients with severe bone disease, 70% showed increased uptake on the initial images, whereas in the other groups, increased uptake was seen only on the delayed images, as expected. CONCLUSION: Our data show a high degree of accuracy for the use of (99m)Tc-sestamibi scanning as a localizing procedure in severe primary hyperparathyroidism.

Is it ethical to use placebos in osteoporosis trials?

The use of placebo control groups (e.g., subjects using calcium and vitamin D) in osteoporosis trials with subjects at high risk for fracture has been systematically questioned by institutional review boards (IRBs). Regulatory agencies, on the other hand, continue to not only recommend but also require that placebo-controlled trials be presented for the registration of new drugs for osteoporosis treatment. The Declaration of Helsinki and its updates have upheld the principle that protection of research subjects' rights is of primary concern. Nevertheless, even the Declaration keeps clearly opening the possibility of using placebo-control designs if it is justified for "compelling and scientifically sound methodological reasons." The use of intermediary endpoints or surrogates to establish the efficacy or safety of new medications in the management of osteoporosis is currently considered scientifically insufficient. This concept has led regulatory agencies, such as the Food and Drug Administration in the United States and the European Medicines Agency in the European Union, to require "fragility fracture reduction" as the primary endpoint in clinical trials for the registration of new drugs. Superiority or noninferiority trials are alternatives to placebo-controlled designs. However, factors such as sample size, cost, and statistical limitations render these models impractical for the registration of new medications for osteoporosis. We recommend collaboration among regulatory agencies, IRBs, scientists, and ethicists on the design of clinical trials for the registration of new medications for reduction of fracture risk. Delay in developing mutually acceptable models may impair scientific development in the field and possibly deprive patients of potentially beneficial treatments.

[Treatment of Paget's disease of bone: importance of the zoledronic acid]. / Tratamento da doença de Paget óssea: importância do ácido zoledrônico.

Paget's disease is a localised monostotic or polyostotic bone disease of unknown origin. It may be caused by a slow viral infection and/or genetic factors. It is characterised by increased bone remodelling and an initially excessive osteoclastic bone resorption, followed by a secondary increase in osteoblastic activity, leading to replacement of the normal bone by a disorganized, enlarged, and weakened osseous structure prone to deformities and fractures. The disease may be diagnosed by radiography, scintigraphy and biochemical tests. The primary aim of treatment is to reduce pain and risk of developing long-term complications. Potent antiresorptive drugs are now available, which control the increased bone remodelling and have led to a dramatic improvement in treatment. Zoledronic acid, a new generation of bisphosphonates, has the advantage of great potency and long duration of remission and a short infusion time.

Vitamin D deficiency: A global perspective.

Vitamin D is essential for the maintenance of good health. Its sources can be skin production and diet intake. Most humans depend on sunlight exposure (UVB 290-315 nm) to satisfy their requirements for vitamin D. Solar ultraviolet B photons are absorbed by the skin, leading to transformation of 7-dehydrocholesterol into vitamin D3 (cholecalciferol). Season, latitude, time of day, skin pigmentation, aging, sunscreen use, all influence the cutaneous production of vitamin D3. Vitamin D deficiency not only causes rickets among children but also precipitates and exacerbates osteoporosis among adults and causes the painful bone disease osteomalacia. Vitamin D deficiency has been associated with increased risk for other morbidities such as cardiovascular disease, type 1 and type 2 diabetes mellitus and cancer, especially of the colon and prostate. The prevalence of hypovitaminosis D is considerable even in low latitudes and should be taken into account in the evaluation of postmenopausal and male osteoporosis. Although severe vitamin D deficiency leading to rickets or osteomalacia is rare in Brazil, there is accumulating evidence of the frequent occurrence of subclinical vitamin D deficiency, especially in elderly people.

From mild to severe primary hyperparathyroidism: The Brazilian experience.

Primary hyperparathyroidism often presents as an asymptomatic disorder. In our institution, routine serum calcium measurements have now been used as part of medical examination for 23 years. Out of 124 patients consecutively seen at our institution, 47% presented with no symptoms related to the disease, while 25% presented with severe skeletal involvement and osteitis fibrosa cystica, 25% with renal stone disease without overt bone involvement, and 2% with the typical neuropsychiatric syndrome. This same pattern is seen in the city of São Paulo. In severe disease pathological fractures are frequently seen, especially in long bones of the lower extremities, and also loss of lamina dura of the teeth and salt-and-pepper appearance of the skull. Bone mineral density is extremely low in these patients but usually show remarkable recovery following surgical cure. Serum PTH and bone markers are considerable higher in severely affected patients, who also have a high rate of vitamin D deficiency, and the parathyroid lesion is easier located compared with asymptomatic patients. From pathological specimens 87% had histological confirmation of a single adenoma, 6.4% multiple gland hyperplasia and 3.8% carcinoma.

Paget's disease of bone.

Paget's disease of bone is a focal disorder of bone remodeling accompanied initially by an increase in bone resorption, followed by a disorganized and excessive formation of bone, leading to pain, fractures and deformities. It exhibits a marked geographical variation in its prevalence. In Brazil it predominantly affects persons of European descent. The majority of the reported cases of the disease in Brazil are from Recife, owing to its peculiar mixed European colonization over approximately four centuries. The etiology is complex and involves both genetic and environmental factors. The disease is often asymptomatic and diagnosis is usually based on biochemical markers of bone turnover, radionuclide bone scan and radiological examination. Bisphosphonates, in particular zoledronic acid, are regarded as the treatment of choice for Paget's disease of bone.

The association between vitamin D receptor gene polymorphisms (TaqI and FokI), Type 2 diabetes, and micro-/macrovascular complications in postmenopausal women.

INTRODUCTION: Since there is evidence of the action of vitamin D as a modulator of insulin release and atherosclerosis, it may well be that the vitamin D receptor polymorphisms are associated with diabetes and its chronic complications. AIMS: To examine the associations between vitamin D receptor polymorphisms (FokI and TaqI) and Type 2 diabetes (T2DM) and its associated chronic complications in postmenopausal women. METHODS: This cross-sectional study analyzed 100 postmenopausal women with T2DM (mean age 65.7±7.18 years) and 100 postmenopausal women without diabetes in the control group (mean age 65.1±9.18 years; P=0.1608). We evaluated clinical and metabolic parameters and analyzed TaqI and FokI polymorphisms. RESULTS: There were no significant differences in genotype and allele frequencies between patients and controls in either of the polymorphisms studied. In the group of patients with diabetes, there were no significant differences in either polymorphism in relation to stroke, retinopathy, nephropathy, or neuropathy. However, in patients with T2DM and coronary artery disease, f genotype (P=0.0361) and the combination of Ff + ff genotypes were observed less frequently (P=0.0462). CONCLUSION: This study suggests the potential protective factor of FokI polymorphism for coronary artery disease in postmenopausal women with T2DM in the recessive model.

The effects of intermittent vitamin D3 supplementation on muscle strength and metabolic parameters in postmenopausal women with type 2 diabetes: a randomized controlled study.

BACKGROUND: The aim of this study was to evaluate the effect of weekly vitamin D3 supplementation on metabolic parameters and muscle strength of postmenopausal women with type 2 diabetes. METHODS: A total of 38 patients with serum 25-hydroxy vitamin D [25(OH)D] below 30 ng/ml and hand strength below 20 kg were randomly assigned to oral vitamin D3 (6600 IU/week in 2 cc oil preparation) or 2 cc olive oil weekly for 3 months. RESULTS: There were nonsignificant increases in serum 25(OH)D in the intervention group to 22.98 ± 4.23 ng/ml and nonsignificant decreases in the control group to 22.84 ± 3.88 (26% of the intervention and 48% of the control groups had 25(OH)D < 20 ng/ml). Handgrip strength improved significantly in the intervention group (right arm 17.4 ± 2.68 to 19.9 ± 3.53 kg, p = 0.002; left arm 16.31 ± 2.6 to 18.46 ± 3.2 kg, p < 0.001) but not in the control group (right arm 16.87 ± 3.99 to 17.93 ± 4.91 kg, p = 0.1; left arm 16.13 ± 4.29 to 16.86 ± 4.79 kg, p < 0.2). More patients in the control group became obese at the end of the study period (p = 0.014). There were no significant changes in mean fasting glucose, glycated haemoglobin (HbA1c), serum triglycerides and blood pressure with vitamin D supplementation. Systolic blood pressure increased significantly in the control group from 136.6 ± 18.6 to 141.4 ± 17.6 mmHg, p = 0.04). CONCLUSIONS: Vitamin D3 supplementation in doses equivalent to 942 IU/day improved isometric handgrip strength, but had no effect on glycaemic control in postmenopausal women with longstanding type 2 diabetes.

Assessment of a glycated hemoglobin point-of-care analyzer (A1CNow+) in comparison with an immunoturbidimetric method: a diagnostic accuracy study.

CONTEXT AND OBJECTIVE: To monitor glycemic control in diabetic patients, regular measurement of glycated hemoglobin (HbA1c) is recommended, but this can be difficult in remote places without access to laboratories. Portable point-of-care testing devices can prove a useful alternative. Our study aimed to assess the performance of one of them: A1CNow+, from Bayer. DESIGN AND SETTING: Cross-sectional accuracy study conducted at a university hospital in Brazil. METHODS: We made three successive measurements of capillary HbA1c using the A1CNow+ in 55 diabetic volunteers, while the same measurement was made on venous blood using the hospital reference method (Vitros 5,1 FS). We used the Bland-Altman graphical method to assess the A1CNow+ in relation to the Vitros 5,1 FS method. We also evaluated clinical usefulness by calculating the sensitivity and specificity of A1CNow+ for detecting patients with HbA1c lower than 7%, which is the usual limit for good glycemic control. RESULTS: The coefficient of variation between repeat testing for the A1CNow+ was 3.6%. The mean difference between A1CNow+ and Vitros 5,1 FS was +0.67% (95% confidence interval, CI: +0.52 to +0.81). The agreement limits of our Bland-Altman graph were -0.45 (95% CI: -0.71 to -0.19) and +1.82 (95% CI: +1.52 to +2.05). The sensitivity and specificity in relation to the 7% limit were respectively 100% and 67.7%. CONCLUSIONS: Although the A1CNow+ had good sensitivity, its accuracy was insufficient for use as a replacement for laboratory measurements of HbA1c, for glycemic control monitoring in diabetic patients.

Relationship between serum vitamin d status and clinical manifestations of primary hyperparathyroidism.

OBJECTIVE: To compare vitamin D status represented by serum 25-hydroxyvitamin D (25-OHD) levels in a group of patients with primary hyperparathyroidism, stratified by clinical manifestations. METHODS: We studied 22 patients (18 women and 4 men) with primary hyperparathyroidism--5 patients with severe osteitis fibrosa cystica, 10 symptomatic patients with active renal stone disease without overt bone disease, and 7 asymptomatic patients. Bone mineral density (BMD) measurements (T-scores) were done at the lumbar spine, femoral neck, and distal radius, and laboratory data for the three subgroups were analyzed. RESULTS: Although considerably younger than the asymptomatic group, patients with osteitis fibrosa had significantly lower mean serum 25-OHD levels (16.7 +/- 1.1 ng/mL versus 29.9 +/- 2.9 ng/mL; P = 0.003). Moreover, patients with osteitis fibrosa had significantly lower BMD in comparison with patients who had renal stone disease as well as asymptomatic patients for all sites measured. Serum parathyroid hormone levels were significantly higher in patients with osteitis fibrosa than in asymptomatic patients (1,352.8 +/- 297.2 pg/mL versus 145.0 +/- 43.7 pg/mL; P<0.02) as well as in comparison with patients who had renal stone disease (P<0.02). Patients with osteitis fibrosa had urinary N-telopeptide levels that were significantly higher than those in asymptomatic patients (501.5 +/- 201.7 versus 51.3 +/- 6.4 nmol/mmol creatinine; P = 0.02) and those in patients with renal stone disease (P = 0.01). CONCLUSION: The findings in this study demonstrate that vitamin D deficiency or insufficiency may contribute to disease severity in primary hyperparathyroidism.

Vitamin D and diabetes mellitus: an update 2013.

Vitamin D deficiency and diabetes mellitus are two common conditions and they are widely prevalent across all ages, races, geographical regions, and socioeconomic conditions. Epidemiologic studies have shown association of vitamin D deficiency and increased risk of chronic diseases, such as cancer, cardiovascular disease, type 2 diabetes, and autoimmune diseases, such as multiple sclerosis and type 1 diabetes mellitus. The identification of 1,25(OH)2D receptors and 1-α-hydroxilase expression in pancreatic beta cells, in cells of the immune system, and in various others tissues, besides the bone system support the role of vitamin D in the pathogenesis of type 2 diabetes. Observational studies have revealed an association between 25(OH) D deficiency and the prevalence of type 1 diabetes in children and adolescents. This review will focus on the concept of vitamin D deficiency, its prevalence, and its role in the pathogenesis and risk of diabetes mellitus and cardiovascular diseases.

Diagnosis and management of Paget's disease of bone.

OBJECTIVE: To conduct a literature review on the diagnosis and management of Paget's disease of bone. MATERIALS AND METHODS: This scientific statement was generated by a request from the Brazilian Medical Association (AMB) to the Brazilian Society of Endocrinology and Metabolism (SBEM) as part of its Clinical Practice Guidelines program. Articles were identified by searching in PubMed and Cochrane databases as well as abstracts presented at the Endocrine Society, Brazilian Society for Endocrinology Annual Meetings and the American Society for Bone and Mineral Research Annual Meeting during the last 5 years. Grading quality of evidence and strength of recommendation were adapted from the first report of the Oxford Centre for Evidence-based Medicine. All grades of recommendation, including "D", are based on scientific evidence. The differences between A, B, C and D, are due exclusively to the methods employed in generating evidence. CONCLUSION: We present a scientific statement on Paget's disease of bone providing the level of evidence and the degree of recommendation regarding causes, clinical presentation as well as surgical and medical treatment.

Prevalence of vitamin D deficiency is higher in patients with Paget's disease of bone compared with age-matched controls.

OBJECTIVE: To investigate if vitamin D deficiency is more prevalent in patients with Paget's disease of bone (PDB) than in age-matched controls. SUBJECTS AND METHODS: We measured serum 25-OHD in 28 untreated patients with PDB and two control groups: 284 elderly men from an ongoing cohort from our department, and 151 postmenopausal women seen in our outpatient clinic for routine medical evaluation. RESULTS: The mean ± SD serum 25-OHD was significantly lower in subjects with PDB (23.76 ± 6.29 ng/mL) than in the control groups of elderly men (27.86 ± 13.52 ng/mL) and postmenopausal women (30.30 ± 9.59 ng/mL), p = 0.015. The prevalence of vitamin D deficiency considering a cut-off point of serum 25-OHD < 30 ng/mL was 85.7% in patients with PDB, and in elderly men and postmenopausal women it was 66.7 % and 54.3%, respectively (p < 0.001). CONCLUSION: These results suggest a high prevalence of hypovitaminosis D in patients with Paget's disease living in the tropics.

Diagnosis and management of primary hyperparathyroidism--a scientific statement from the Department of Bone Metabolism, the Brazilian Society for Endocrinology and Metabolism.

OBJECTIVE: To conduct a literature review on the diagnosis and management of primary hyperparathyroidism including the classical hipercalcemic form as well as the normocalcemic variant. MATERIALS AND METHODS: This scientific statement was generated by a request from the Brazilian Medical Association (AMB) to the Brazilian Society for Endocrinology as part of its Clinical Practice Guidelines program. Articles were identified by searching in PubMed and Cochrane databases as well as abstracts presented at the Endocrine Society, Brazilian Society for Endocrinology Annual Meetings and the American Society for Bone and Mineral Research Annual Meeting during the last 5 years. Grading quality of evidence and strength of recommendation were adapted from the first report of the Oxford Centre for Evidence-based Medicine. All grades of recommendation, including "D", are based on scientific evidence. The differences between A, B, C and D, are due exclusively to the methods employed in generating evidence. CONCLUSION: We present a scientific statement on primary hyperparathyroidism providing the level of evidence and the degree of recommendation regarding causes, clinical presentation as well as surgical and medical treatment.

Normocalcemic primary hyperparathyroidism in clinical practice: an indolent condition or a silent threat?

OBJECTIVE: To describe the characteristics of normocalcemic primary hyperparathyroidism (NPHPT) in patients seen for osteoporosis evaluation. PATIENTS AND METHODS: We examined the records of 156 women who came to the hospital to be screened for osteoporosis. Measurements of total calcium, PTH, 25-hydroxy vitamin D, and ß-C-telopeptide were recorded. Bone mineral density and T-scores were evaluated by densitometry of the lumbar spine, femoral neck and distal one-third of the radius. The latter was only measured in patients with primary hyperparathyroidism. Nephrolithiasis and bone fractures were documented by a review of the medical records. RESULTS: We identified 14 patients with NPHPT, accounting for 8.9% of the population studied. In the medical records, the occurrence of kidney stones was reported in 28.6% of the patients with NPHPT, in contrast with only 0.7% of the noncarriers. Regarding the presence of general fractures, 21.4% of the patients with NPHPT were affected versus 16.2% of noncarriers. CONCLUSION: Data from our study suggest that NPHPT has a diverse phenotypic presentation, implying that this may not be an "indolent" disease.