The usefulness of bone metabolic indices for the prediction of changes in bone mineral density after parathyroidectomy in patients with primary hyperparathyroidism.

Patients with primary hyperparathyroidism (pHPT) have reduced bone mineral density (BMD). Although pHPT causes high bone turnover, the exact metabolic bone markers useful for predicting changes in BMD after parathyroidectomy (PTX) remain elusive. The present study was performed to examine the relationship between bone metabolic indices and BMD changes after PTX in 29 pHPT Japanese patients, which received PTX successfully. BMD values were measured by dual-energy X-ray absorptiometry in the lumbar spine and distal one third of radius. As for bone metabolic indices, serum bone-type alkaline phosphates (BAP), serum osteocalcin (OCN), urinary deoxypiridinoline (Dpd), and urinary type I collagen cross-linked N-telopeptides (NTX) were measured. The study included 10 male and 19 female patients (17 postmenopausal). Urinary Dpd, but not NTX was significantly correlated with serum BAP and OCN. Either bone formation or bone resorption indices were significantly and highly correlated with Z-score of BMD in the radius, but not at lumbar spine. Urinary Dpd was significantly correlated with BMD changes at both lumbar spine and radius and at all time points over the two years after PTX. These correlations were most potent among bone metabolic indices in this study. The measurement of urinary Dpd would be useful for predicting long-term changes in BMD at radial and lumbar spine after PTX than other bone metabolic indices.     

Effects of nasal calcitonin on bone mineral density following parathyroidectomy in patients with primary hyperparathyroidism

AIM: To investigate whether nasal salmon calcitonin (CT; 200 U/day) given in addition to calcium helps to restore the bone mass after parathyroidectomy (PTX) in patients with primary hyperparathyroidism (PHPT). METHODS: Twenty patients with PHPT were enrolled after successful PTX and received 1 g calcium per os daily for 1 year. They were randomly assigned either to nasal CT (CT group) or to no treatment. The bone mass was measured using dual-energy X-ray absorptiometry at multiple sites. RESULTS: Eight patients in each group completed the study. After 12 months, the bone mass increased significantly at whole-body level and at lumbar spine in both groups, increased at hip and epiphyses of tibia or radius in the CT group only, and did not change at diaphyses of tibia and radius in either group. CONCLUSIONS: Bone mass increases after PTX for PHPT in patients receiving oral calcium. CT may help to restore the bone mass at sites of the appendicular skeleton, where trabecular bone predominates.     

Alendronate increases bone mineral density in patients with symptomatic primary hyperparathyroidism

Primary hyperparathyroidism (PHPT) is often associated with low bone mineral density (BMD). An open-labeled, prospective trial was conducted to determine whether alendronate (ALN), 10 mg daily, maintains or improves BMD in patients with advanced PHPT. All patients had symptomatic PHPT and met surgical guidelines however refused surgery. Nineteen patients was treated with alendronate for 2 years. The primary outcome index, BMD, was measured at the lumbar spine (LS) and femoral neck (FN) every 6 months by dual-energy x-ray absorptiometry. Serum calcium, phosphorous and PTH, and urinary calcium excretion were monitored every 3 months. Treatment with alendronate over 2 years was associated with a significant (5.3+/-0.4%; p<0.01) increase in LS BMD in comparison with baseline. FN BMD increased significantly at 24 months with alendronate by 2.5%+/-0.7 (p<0.01) from baseline. Serum calcium, phosphorus and PTH, and urine calcium excretion did not change with alendronate therapy. In PHPT, alendronate significantly increases BMD at the LS and FN at 24 months from baseline values with stable serum calcium and PTH levels. Alendronate may be a useful alternative to parathyroidectomy in symptomatic PHPT among those with low BMD, who are candidates for surgery but either decline or for whom surgery is contraindicated.     

Normal responsiveness of serum parathyroid hormone to beta-adrenergic blockade in patients with secondary hyperparathyroidism

Infusion of calcium gluconate (15 mg Ca++/kg body weight in 4 h) to 6 patients with secondary hyperparathyroidism (due to mild renal insufficiency) decreased serum parathyroid hormone (PTH) levels to the same degree (on a percent basis) as in normal subjects. Serum PTH values at 4 h were 60 +/- 4.5 (SEM)% of baseline in the patients and 59 +/- 2.9% of baseline in the normal subjects. Infusion of propranolol (1 mg i.v. bolus followed by an infusion of 60 micrograms/min for 2 h) to 7 additional patients with secondary hyperparathyroidism also decreased serum PTH to the same degree as in normal subjects. Serum PTH values at 2 h were 68 +/- 10.4% of baseline in the patients and 68 +/- 3.3% of baseline in the normal subjects. The studies indicate normal responsiveness of serum PTH to calcium or beta-adrenergic blockade in secondary hyperparathyroidism due to mild renal insufficiency.     

Vitamin d status and its relationship with bone mineral density and parathyroid hormone in southeast asian adults with low bone density

ObjectiveTo investigate the vitamin D sufficiency status and the relationships among serum 25-hydroxyvitamin D [25(OH)D] levels, intact parathyroid hormone (iPTH) levels, and bone mineral density (BMD) in patients attending an osteoporosis clinic in Singapore.MethodsIn total, 193 adults with or without prevalent fragility fractures and with low BMD at the femoral neck, total hip, or lumbar spine underwent assessment. Multivariate regression models were used to investigate the relationships among serum 25(OH)D, iPTH, and BMD.ResultsThe mean values (standard deviation) for age of the patients and serum 25(OH)D level were 61 (14) years and 26.05 (7.97) ng/mL, respectively. In 72% of patients, serum 25(OH)D levels were below 30 ng/mL. There was no association between 25(OH)D levels and BMD at the femoral neck, total hip, or lumbar spine(P = .568, .461, and .312, respectively). Serum iPTH levels were negatively associated with BMD at the total hip(P = .035) and the lumbar spine (P = .019). At levels < 30 ng/mL, 25(OH)D was negatively associated with iPTH (P = .036).ConclusionAmong this Southeast Asian population of patients with low BMD, no direct relationship between serum 25(OH)D levels and BMD was observed. A negative correlation existed, however, between iPTH and 25(OH)D at serum 25(OH)D concentrations < 30 ng/mL, and serum iPTH levels showed a significant negative association with BMD at the total hip and lumbar spine. These significant negative associations between iPTH levels and BMD at the total hip and lumbar spine underscore the critical role of this hormone in bone metabolism and health. (Endocr Pract. 2011;17:226-234)     

Surgical treatment of secondary hyperparathyroidism in patients with chronic renal failure: reevaluation of indications for parathyroidectomy

On reviewing the preoperative clinical and laboratory findings and the surgical response seen in our series of 32 patients with renal hyperparathyroidism, the indication for parathyroidectomy was reevaluated. During the 5-year period from 1975 to 1979, parathyroid resection was performed in 9 patients who had various conditions for which surgery had been thought indicated. During the following period from January 1980 to March 1985, parathyroidectomy was carried out on 23 patients all of whom had roentgenologic evidence of generalized fibrous osteitis except for two whose indication for surgery was an elevation of the serum alkaline phosphatase level more than 45 KA units. The resected parathyroid glands had increased to 1 g or more in total weight in all the 25 patients who showed distinct postoperative improvement. Laboratory evidence indicating the presence of generalized fibrous osteitis, such as subperiosteal resorption on phalanx roentgenograms and high serum alkaline phosphatase level, along with marked elevation of the plasma immunoreactive parathyroid hormone level, proved to be a good indicator for medically uncontrollable secondary hyperparathyroidism. Fracture, heterotopic calcification, pruritus or persistent hypercalcemia was not a parameter of severe hyperparathyroidism warranting parathyroid resection, unless there was concomitant evidence of fibrous osteitis. The preoperative use of the recently developed noninvasive techniques for parathyroid localization also proved to be useful in detecting the parathyroid glands large enough to fulfill the requirements for parathyroidectomy.     

Radioimmunoassay for human parathyroid hormone for differentiation between patients with hypoparathyroidism, hyperparathyroidism and normals.

A RIA system for human PTH is presented using a goat antibody (Code name 017-spring-78) against C-terminal hPTH fragments, as well as a human PTH standard from hemodiafiltration of a hyperparathyroid patient. It proved to be useful for the differentiation not only between hyperparathyroid patients and normals, but even within the normal range and hypoparathyroid states.     

Effect of eplerenone on parathyroid hormone levels in patients with primary hyperparathyroidism: a randomized, double-blind, placebo-controlled trial

ABSTRACT: BACKGROUND: Increasing evidence suggests the bidirectional interplay between parathyroid hormone and aldosterone as an important mechanism behind the increased risk of cardiovascular damage and bone disease observed in primary hyperparathyroidism. Our primary object is to assess the efficacy of the mineralocorticoid receptor-blocker eplerenone to reduce parathyroid hormone secretion in patients with parathyroid hormone excess. Methods/design Overall, 110 adult male and female patients with primary hyperparathyroidism will be randomly assigned to eplerenone (25 mg once daily for 4 weeks and 4 weeks with 50 mg once daily after dose titration] or placebo, over eight weeks. Each participant will undergo detailed clinical assessment, including anthropometric evaluation, 24-h ambulatory arterial blood pressure monitoring, echocardiography, kidney function and detailed laboratory determination of biomarkers of bone metabolism and cardiovascular disease. The study comprises the following exploratory endpoints: mean change from baseline to week eight in (1) parathyroid hormone(1--84) as the primary endpoint and (2) 24-hour systolic and diastolic ambulatory blood pressure levels, NT-pro-BNP, biomarkers of bone metabolism, 24 hours urinary protein/albumin excretion and echocardiographic parameters reflecting systolic and diastolic function as well as cardiac dimensions, as secondary endpoints. DISCUSSION: In view of the reciprocal interaction between aldosterone and parathyroid hormone and the potentially ensuing target organ damage, the EPATH trial is designed to determine whether eplerenone, compared to placebo, will effectively impact on parathyroid hormone secretion and improve cardiovascular and bone health in patients with primary hyperparathyroidism. Trial registration ISRCTN33941607.     

Automated determination of bone age and bone mineral density in patients with juvenile idiopathic arthritis: a feasibility study

Introduction

Chronic inflammation combined with glucocorticoid treatment and immobilization puts juvenile idiopathic arthritis (JIA) patients at risk of impaired growth and reduced bone mineral density (BMD). Conventional methods for evaluating bone age and BMD are time-consuming or come with additional costs and radiation exposure. In addition, an automated measurement of bone age and BMD is likely to be more consistent than visual evaluation. In this study, we aimed to evaluate the feasibility of an automated method for determination of bone age and (cortical) bone mineral density (cBMD) in severely affected JIA patients. A secondary objective was to describe bone age and cBMD in this specific JIA population eligible for biologic treatment.

Methods

In total, 69 patients with standard hand radiographs at the start of etanercept treatment and of calendar age within the reliability ranges (2.5 to 17 years for boys and 2 to 15 years for girls) were extracted from the Dutch Arthritis and Biologicals in Children register. Radiographs were analyzed using the BoneXpert method, thus automatically determining bone age and cBMD expressed as bone health index (BHI). Agreement between measurements of the left- and right-hand radiographs and a repeated measurement of the left hand were assessed with the intraclass correlation coefficient (ICC). Regression analysis was used to identify variables associated with Z-scores of bone age and BHI.

Results

The BoneXpert method was reliable in the evaluation of radiographs of 67 patients (radiographs of 2 patients were rejected because of poor image quality). Agreement between left- and right-hand radiographs (ICC = 0.838 to 0.996) and repeated measurements (ICC = 0.999 to 1.000) was good. Mean Z-scores of bone age (−0.36, P = 0.051) and BHI (−0.85, P < 0.001) were lower compared to the healthy population. Glucocorticoid use was associated with delayed bone age (0.79 standard deviation (SD), P = 0.028), and male gender was associated with a lower Z-score of BHI (0.65 SD, P = 0.021).

Conclusions

BoneXpert is an easy-to-use method for assessing bone age and cBMD in patients with JIA, provided that radiographs are of reasonable quality and patients’ bone age lies within the age ranges of the program. The population investigated had delayed bone maturation and lower cBMD than healthy children.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-014-0424-1) contains supplementary material, which is available to authorized users.     

Impact of intra- and extra-osseous soft tissue composition on changes in bone mineral density with weight loss and regain

Recent studies report a significant gain in bone mineral density (BMD) after diet-induced weight loss. This might be explained by a measurement artefact. We therefore investigated the impact of intra- and extra-osseous soft tissue composition on bone measurements by dual X-ray absorptiometry (DXA) in a longitudinal study of diet-induced weight loss and regain in 55 women and 17 men (19-46 years, BMI 28.2-46.8 kg/m(2)). Total and regional BMD were measured before and after 12.7 ± 2.2 week diet-induced weight loss and 6 months after significant weight regain (≥30%). Hydration of fat free mass (FFM) was assessed by a 3-compartment model. Skeletal muscle (SM) mass, extra-osseous adipose tissue, and bone marrow were measured by whole body magnetic resonance imaging (MRI). Mean weight loss was -9.2 ± 4.4 kg (P < 0.001) and was followed by weight regain in a subgroup of 24 subjects (+6.3 ± 2.9 kg; P < 0.001). With weight loss, bone marrow and extra-osseous adipose tissue decreased whereas BMD increased at the total body, lumbar spine, and the legs (women only) but decreased at the pelvis (men only, all P < 0.05). The decrease in BMD(pelvis) correlated with the loss in visceral adipose tissue (VAT) (P < 0.05). Increases in BMD(legs) were reversed after weight regain and inversely correlated with BMD(legs) decreases. No other associations between changes in BMD and intra- or extra-osseous soft tissue composition were found. In conclusion, changes in extra-osseous soft tissue composition had a minor contribution to changes in BMD with weight loss and decreases in bone marrow adipose tissue (BMAT) were not related to changes in BMD.     

Comparison of total parathyroidectomy without autotransplantation and without thymectomy versus total parathyroidectomy with autotransplantation and with thymectomy for secondary hyperparathyroidism: TOPAR PILOT-Trial

Introduction

The clinical significance of a treatment effect demonstrated in a randomized trial is typically assessed by reference to differences in event rates at the group level. An alternative is to make individualized predictions for each patient based on a prediction model. This approach is growing in popularity, particularly for cancer. Despite its intuitive advantages, it remains plausible that some prediction models may do more harm than good. Here we present a novel method for determining whether predictions from a model should be used to apply the results of a randomized trial to individual patients, as opposed to using group level results.

Methods

We propose applying the prediction model to a data set from a randomized trial and examining the results of patients for whom the treatment arm recommended by a prediction model is congruent with allocation. These results are compared with the strategy of treating all patients through use of a net benefit function that incorporates both the number of patients treated and the outcome. We examined models developed using data sets regarding adjuvant chemotherapy for colorectal cancer and Dutasteride for benign prostatic hypertrophy.

Results

For adjuvant chemotherapy, we found that patients who would opt for chemotherapy even for small risk reductions, and, conversely, those who would require a very large risk reduction, would on average be harmed by using a prediction model; those with intermediate preferences would on average benefit by allowing such information to help their decision making. Use of prediction could, at worst, lead to the equivalent of an additional death or recurrence per 143 patients; at best it could lead to the equivalent of a reduction in the number of treatments of 25% without an increase in event rates. In the Dutasteride case, where the average benefit of treatment is more modest, there is a small benefit of prediction modelling, equivalent to a reduction of one event for every 100 patients given an individualized prediction.

Conclusion

The size of the benefit associated with appropriate clinical implementation of a good prediction model is sufficient to warrant development of further models. However, care is advised in the implementation of prediction modelling, especially for patients who would opt for treatment even if it was of relatively little benefit.     

DNA ploidy pattern of parathyroid parenchymal cells in renal secondary hyperparathyroidism with relapse.

The nuclei of parathyroid parenchymal cells, analyzed using image cytometry (ICM), in relapsing and non-relapsing secondary hyperparathyroidism due to uremia, showed a DNA-distribution pattern of diploid type. Nevertheless, some differences were observed within the groups, as regards the concept of 'scattered cells' in ICM DNA histograms. The relative incidence of 'scattered cells' was particularly high in the histograms from parathyroid glands with nodular hyperplasia and in those from parathyroid parenchyma grafted into the skeletal musculature. In these two kinds of parathyroid specimens, the 'scattered cells' were both of chief-cell and oxyphil-cell types. In contrast, 'scattered cells' were not so conspicuous when parenchymal cells of glands with diffuse hyperplasia were analyzed. As there is some clinical and histopathological evidence that the cells in both nodular-hyperplastic and autografted parathyroid parenchyma have increased growth potential, it is hypothesized that the relative incidence of the 'scattered cells' in the ICM DNA histograms indicates an increased proliferative activity.     

Longitudinal measurement of bone mineral density at the radius in hemodialysis patients using dual-energy X-ray absorptiometry

The object of our study was to document the changes in bone mineral density (BMD) at the (1/3) distal radius in patients undergoing maintenance hemodialysis (HD). Forty nine male and 24 female patients were enrolled in this study. The mean age was 55.9-/+13.1 (mean -/+ SD) years, and the duration of HD was 89.2 -/+ 81.0 months at the beginning of the investigation. BMD was measured by dual-energy X-ray absorptiometry at 1-year intervals for a period in excess of 3 years. No significant relationship was observed between BMD and age in both sexes. In male patients, BMD was positively correlated with body mass index (BMI) (r=0.47, p<0.01) and negatively with the duration of HD (r=0.61, p<0.01). In contrast, BMD was not correlated with either BMI or with the duration of HD in female patients. Eleven of the 14 patients on HD for more than 15 years showed marked bone loss (male; 0.460, female; 0.394g/cm(2)), although they were relatively young (mean age: 43.4 years). Prolonged HD could be one of the risk factors responsible for bone loss.     

Effect of misoprostol on bone mineral density in women with postmenopausal osteoporosis

OBJECTIVE: To evaluate the effect of misoprostol on bone mineral density in postmenopausal women. MATERIALS AND METHODS: The study was performed in a randomized controlled prospective manner in 90 women with menopause at Süleymaniye Maternity and Women's Diseases Teaching and Research Hospital between January and December 2003. Cases were divided into three groups each consisting of 30 women who were in menopause for at least 1 year and had t-scores less than -1 by dual energy X-ray densitometry (DEXA). Group I was treated with misoprostol and calcium, Group II received tibolone and calcium and Group III was given calcium only and considered as control group. In all patients, bone mineral density in L1-L4 vertebrae, femur neck and Ward triangle were measured by DEXA and t and z scores were calculated. RESULTS: All groups were similar demographically. Bone mineral density in L1-L4 vertebrae, femur neck and Ward triangle in the group treated with misoprostol, increased by 5, 8.1 and 3.6%, respectively. In the tibolone group, bone mineral density in L1-L4 vertebrae, femur neck and Ward triangle increased by 8.3, 5.3 and 7.8%, respectively. There was not a significant difference in t and z-scores and bone mineral density measurements between misoprostol and tibolon groups. CONCLUSION: Misoprostol may be an alternative treatment for patients with osteopenia and osteoporosis who are not suitable for hormone replacement therapy.     

Effect of alendronate administration on bone mineral density and bone strength in castrated rats.

Castration of male rats leads to increased bone turnover and osteopenia. This study was conducted to examine the effects of the aminobisphosphonate alendronate on castration-induced bone changes. Bisphosphonates are drugs that inhibit bone turnover by decreasing the resorption. Since they suppress bone remodeling, they may also prevent the repair of microdamage and decrease bone strength. Although the mechanical properties of bones are directly related to the determination of fracture risk, bisphosphonate effects on the related variables have scarcely been investigated. Twenty-four male Wistar rats at two months of age were castrated or sham-operated to evaluate the effects of long-term administration (six months) of sodium alendronate at a dose of 1 mg/kg/day. The bones were tested mechanically by a three-point bending test in a Mini Bionix (MTS) testing system. High bone remodeling seen in castrated rats expressed by increased TrACP and B-ALP was suppressed by alendronate administration. Bone from castrated rats was characterized by a reduction in bone density as well as ash, calcium and phosphate content. Castration significantly altered mechanical properties of bone and femoral cortical thickness. When castrated rats were treated with high dose of alendronate, the changes in bone density resulting from castration were entirely prevented, and mechanical analysis revealed preserved mechanical strength of femur and cortical thickness. We conclude that castration induces cortical bone loss associated with high bone turnover in the male rat, and this bone loss can be prevented by alendronate through the inhibition of osteoclastic activity, while preserving the mechanical properties of bone. These results document the efficacy of alendronate, even at high doses, in preventing bone loss, loss of bone mechanical strength, and the rise in biochemical bone turnover indicators due to castration in rats, and raises the possibility that a alendronate could be equally effective in humans.     

Effect of low-repetition jump training on bone mineral density in young women.

The hypothesis of the present study was that low-repetition and high-impact training of 10 maximum vertical jumps/day, 3 times/wk would be effective for improving bone mineral density (BMD) in ordinary young women. Thirty-six female college students, with mean age, height, and weight of 20.7+/-0.7 yr, 158.9+/-4.6 cm, and 50.4+/-5.5 kg, respectively, were randomly divided into two groups: jump training and a control group. After the 6 mo of maximum vertical jumping exercise intervention, BMD in the femoral neck region significantly increased in the jump group from the baseline (0.984+/-0.081 vs. 1.010+/-0.080 mg/cm2; P<0.01), although there was no significant change in the control group (0.985+/-0.0143 vs. 0.974+/-0.134 mg/cm2). And also lumbar spine (L2-4) BMD significantly increased in the jump training group from the baseline (0.991+/-0.115 vs. 1.015+/-0.113 mg/cm2; P<0.01), whereas no significant change was observed in the control group (1.007+/-0.113 vs. 1.013+/-0.110 mg/cm2). No significant interactions were observed at other measurement sites, Ward's triangle, greater trochanter, and total hip BMD. Calcium intakes and accelometry-determined physical daily activity showed no significant difference between the two groups. From the results of the present study, low-repetition and high-impact jumps enhanced BMD at the specific bone sites in young women who had almost reached the age of peak bone mass.