Treatment of osteoporosis with TheraCyte-encapsulated parathyroid cells: a study in a rat model

Introduction The purpose of this study was to evaluate parathyroid function at monthly intervals following the implantation of TheraCyte-encapsulated live human parathyroid cells into ovariectomized rats and to determine the effect on bone mineral density (BMD) 4 months after ovariectomy ( 3 months after implantation). Methods Parathyroid tissues were obtained from patients undergoing surgery for secondary hyperparathyroidism. In total, 21 Sprague-Dawley rats divided randomly into three groups were subjected to one of three treatments: (1) implanted with TheraCyte A-encapsulated 4×10⁶ live parathyroid cells; (2) implanted with TheraCyte B-encapsulated 4×10⁵ live parathyroid cells; (3) a sham operation; the control group. Rats were ovariectomized 1 month prior to the implantation of the TheraCyte. Blood was drawn at the time of implantation and at monthly intervals thereafter for 3 months to check the levels of calcium, phosphorus and intact parathyroid hormone (iPTH). The BMD of the lumbar spine (L1–L5) and of the left femoral bone was measured with dual-energy-X-ray absorptiometry (DEXA) 1 month after ovariectomy and 3 months after implantation of the TheraCyte (4 months after ovariectomy). Results We found that the viability ratio of cryopreserved tissues was between 55 and 79% after thawing. In the control group, the BMD of the lumbar spine (L1–L5) had not decreased significantly (p=0.237) nor had the BMD of the left femoral bone increased significantly (p=0.063) 3 months after implantation. In the TheraCyte A group, the BMD of both the lumbar spine (p=0.018) and left femoral bone (p=0.018) had increased significantly 3 months after implantation. In the TheraCyte B group, the BMD of both the lumbar spine (p=0.017) and the left femoral bone (p=0.025) had also increased significantly 3 months after implantation. Serum iPTH levels were higher in the TheraCyte A group than in the TheraCyte B group (p=0.006), and higher in the TheraCyte B group than in the control group (p=0.040). Serum calcium levels were not significantly higher in the TheraCyte group A than in the TheraCyte B group or in the control group. Serum phosphorus levels were not significantly different between the TheraCyte A and TheraCyte B groups. Conclusions Implantation of TheraCyte A-encapsulated 4×10⁵ live parathyroid cells and TheraCyte B-encapsulated 4×10⁶ cells can increase the BMD of ovariectomized rats within 3 months of implantation. Neither cause high serum calcium and low phosphorus concentrations.     

Carotid intima media thickness, oxidative stress, and inflammation in children with chronic kidney disease

Objective

We evaluated the association between inflammation and oxidative stress with carotid intima media thickness (cIMT) and elasticity increment module (E_inc) in pediatric patients with chronic kidney disease (CKD).

Methods

This analytical, cross-sectional study assessed 134 children aged 6–17 years with CKD. Anthropometric measurements and biochemistry of intact parathyroid hormone (iPTH), high-sensitivity C-reactive protein (CRP), interleukin (IL)-6, IL-1β, reduced glutathione (GSH), malondialdehyde, nitric oxide, and homocysteine were recorded. Bilateral carotid ultrasound (US) was taken. Patients were compared with controls for cIMT and E_inc using?≥?75  percentile (PC).

Results

Mean cIMT was 0.528?±?0.089 mm; E_inc was 0.174?±?0.121 kPa × 10³; cIMT negatively correlated with phosphorus (r ?0.19, p?=?0.028) and the calcium × phosphorus (Ca × P) product (r ?0.26, p?=?0.002), and positively with iPTH (r 0.19,p?=?0.024). After adjusting for potential confounders, hemodialysis (HD) (β?=?0.111, p?=?<0.001), automated peritoneal dialysis (APD) (β?=?0.064, p?=?0.026), and Ca x P product (β?=??0.002, p?=?0.015) predicted cIMT (R ²?=?0.296). In patients on dialysis, HD (β?=?0.068, p?=?0.010), low-density lipoprotein cholesterol (LDL-C) (β?=?0.001, p?=?0.048), and GSH (β?=??0.0001, p?=?0.041) independently predicted cIMT (R ²?=?0.204); HD, hypoalbuminemia, and high iPTH increased the risk of increased cIMT. In dialysis, E_inc was inversely associated with GSH, and in predialysis, Ca × P correlated with/predicted E_inc (β?=?0.001, p?=?0.009).

Conclusions

cIMT and E_inc strongly associate with several biochemical parameters and GSH but not with other oxidative stress or inflammation markers.     

Is high-dose cholecalciferol justified in children with chronic kidney disease who failed low-dose maintenance therapy?

Background

We aimed to investigate the effect of single, high-dose intramuscular cholecalciferol on vitamin D3 and intact parathyroid hormone (iPTH) levels in children with chronic kidney disease (CKD).

Methods

Between January 2012 and June 2012, we conducted a prospective, uncontrolled study at the Pediatric Nephrology Unit of King Abdulaziz University Hospital, Jeddah, to investigate the effect of single, high-dose intramuscular vitamin D3 on 25(OH)D3 and iPTH levels in vitamin D insufficient/deficient children with CKD. Serum vitamin D3, iPTH, calcium, phosphate, alkaline phosphatase (ALP), and creatinine levels were measured before intramuscular vitamin D3 (300,000 IU) administration, and these were subsequently repeated at 1 and 3 months after treatment. Statistical analysis was performed with the Statistical Package for the Social Sciences (SPSS Inc., Chicago, IL, USA).

Results

Nineteen children fulfilled the criteria. At 3 months after treatment, vitamin D3 levels were significantly higher than at baseline (p?<?0.001) but lower than the levels at 1 month. iPTH levels decreased significantly at 3 months (p?=?0.01); however, the drop in iPTH levels was not significant at 1 month (p?=?0.447). There were no changes in calcium, phosphate, ALP, or creatinine levels after treatment.

Conclusions

Single-dose intramuscular vitamin D3 (300,000 IU) resulted in significant improvement of vitamin D3 and iPTH levels in children with CKD.     

Bone mineral density and parathyroid function in patients on maintenance hemodialysis

Background

The relationship between parathyroid function, an important determinant of bone turnover, and bone mineral density (BMD) in patients with chronic kidney disease is not fully understood. We wanted to analyze the association between BMD and parathyroid function in hemodialysis patients in details.

Methods

In a cross-sectional design, data from 270 patients (age 55 ± 15 years, 60% men, all Caucasian) on maintenance hemodialysis were analyzed. All patients underwent dual energy X-ray absorptiometry of the lumbar spine (LS), femoral neck (FN) and distal radius (DR). In addition to routine laboratory tests, blood samples were collected for iPTH, serum markers of bone metabolism (alkaline phosphatase, type I collagen crosslinked-C-telopeptide) and 25OH vitamin D.

Results

Based on Z-scores, bone mineral density was moderately reduced only at the femoral neck in the total cohort. The average Z-score of the ??low PTH?? group (iPTH < 100 pg/ml) was not different from the Z-score of patients with iPTH in the ??target range?? (100?C300 pg/ml) at any measurement site. While iPTH was negatively correlated with BMD at all measurement sites in patients with iPTH > 100 pg/ml (rho = ?0.255, ?0.278 and ?0.251 for LS, FN and DR, respectively, P < 0.001 for all), BMD was independent of iPTH in patients with iPTH < 100 pg/ml. Furthermore, iPTH was not associated with serum markers of bone metabolism, but these markers were negatively correlated with BMD in the ??low PTH?? group.

Conclusions

Low PTH levels are not associated with low BMD in patients with end-stage kidney disease. Furthermore, bone metabolism seems to be independent of iPTH in patients with relative hypoparathyroidism likely reflecting skeletal resistance to PTH.     

The Deleterious Effect of Bariatric Surgery on Cortical and Trabecular Bone Density in the Femurs of Non-obese, Type 2 Diabetic Goto-Kakizaki Rats

Background

The effects of type 2 diabetes on bone mass and microstructure are not clear. The aim of this study was to evaluate bone microstructural properties and volumetric bone mineral density (vBMD) in type 2 diabetic Goto-Kakizaki non-obese rats after gastrojejunal bypass and their relationship with hormonal parameters.

Methods

We designed an experimental study in Goto-Kakizaki rats with and without gastrojejunal bypass, performing densitometric and microstructural studies of the distal femur using X-ray computed microtomography (micro-CT). Levels of insulin, glucagon, leptin, and glucagon-like peptide-1 (GLP-1) were also determined.

Results

We observed reduced cortical (1,488.92?±?98.2 vs. 1,727.92?±?133.45?mg/cm³, p?=?0.028) and trabecular (180.8?±?9 vs. 261.23?±?45.54?mg/cm³, p?=?0.036) vBMD in operated rats. Bone volume fraction (BV/TV) and trabecular connectivity were reduced in operated rats, while there was a reduction in cortical thickness and an increase in rod-like trabeculae at the expense of plate-like trabeculae. Leptin was reduced (1,042?±?549 vs. 2,447?±?1,035?pg/ml, p?=?0.05) and GLP-1 increased (1.62?±?0.32 vs. 0.96?±?0.1?ng/ml, p?=?0.008) but only leptin showed a significant association with vBMD

Conclusions

In type 2 diabetic Goto-Kakizaki rats, gastrojejunal bypass produces a reduction in cortical and trabecular bone mineral density and a deterioration in bone quality that could be explained, in part, by the reduction in leptin levels.     

No change in calcium absorption in adult Pakistani population before and after vitamin D administration using strontium as surrogate

Summary

Vitamin D, parathyroid hormone levels and calcium absorption was assessed before and after cholecalciferol using Strontium as a surrogate. Increase in 25OHD, lowering of iPTH with no effect on Sr absorption was seen, suggesting the possibility that maximal Ca absorption had already been achieved in these volunteers.

Introduction

This paper discusses the determination of calcium (Ca) absorption, using strontium (Sr) as a surrogate, before and after a single IM injection of vitamin D₃ (600,000 IU).

Methods

Baseline serum 25-hydroxyvitamin D (25OHD), Sr, Ca, P, and intact parathyroid hormone (iPTH) were determined in 53 fasting volunteers, followed by administrating (PO) 0.03 mM (4.8 mg/kg) SrCl₂ and collecting blood at 0.5, 1 and 4 h to determine the absorption (AUC_0→t ) of Sr. Following the initial absorption test, volunteers received a single IM injection of 600,000 IU vitamin D₃. Two months later, the fasting serum and the Sr absorption test were repeated, as described above.

Results

The IM injection of vitamin D₃ caused a significant increase in fasting 25OHD (from 43.5?±?19 to 66.1?±?19.1 nmol/L (p?<?0.001)) and a trend toward lower serum iPTH (from 59.8?±?27.8 to 53?±?31 ng/L). Fasting serum Ca and P remained unchanged. A higher 25OHD level failed (p?=?0.32) to translate into a higher rate of Sr absorption. AUC_0→4 h were almost identical before and after the IM injection of vitamin D₃.

Conclusion

A single vitamin D₃ injection of 600,000 IU significantly increase mean 25OHD concentration and tended to lower iPTH concentrations in volunteers with initially low 25OHD status, suggesting to utilize this simple form of treatment to improve vitamin D status and to have a possible biological effect on Ca homeostasis. However, we found no obvious effect on Sr absorption, suggesting the possibility that maximal vitamin D-dependent Ca absorption had already been achieved in these volunteers at a lower vitamin D status.     

Vitamin D status of children receiving chronic dialysis

Background

Patients receiving chronic dialysis therapy are presumed to be at risk for 25(OH) D₃ deficiency, but little information is available on its prevalence, manifestations of deficiency, and the impact of ergocalciferol supplementation.

Methods

A single-center, retrospective study of 51 prevalent pediatric patients on hemodialysis or peritoneal dialysis was conducted to address these issues.

Results

Forty of 51 (78.4 %) patients had low (<30 ng/ml) 25(OH) D₃ levels. Of these, 2 % had values?12 years, non-Caucasian race and?>?12-month duration of dialysis were significantly associated with low 25(OH) D₃ levels (p?=?0.006, p?=?0.05, and p?=?0.04, respectively). Twenty-three of the 40 patients deficient in 25(OH) D₃ received repletion therapy with ergocalciferol and had a follow-up level at an average of 2 months following completion of a single course of therapy; 14 (60 %) of the levels were normal. Mean baseline intact parathyroid hormone (iPTH) for patients with 25(OH) D₃ levels?≤?30 was 478.68?±?474.01 pg/ml and treatment with ergocalciferol was not associated with a significant decrease in the mean iPTH value (p?=?0.45).

Conclusions

We conclude that low 25(OH) D₃ levels are common in pediatric patients receiving dialysis and require attention in accordance with current practice guidelines.     

An open-label study to evaluate a single-dose of cinacalcet in pediatric dialysis subjects

Background

There is limited knowledge of the effectiveness and safety profile of cinacalcet in pediatric patients with secondary hyperparathyroidism (sHPT) treated with dialysis.

Methods

This was an open-label, single-dose study conducted on 12 pediatric subjects with chronic kidney disease treated with dialysis. Subjects were stratified by four age cohorts and given a single 15-mg oral dose of cinacalcet. Multiple blood samples were collected up to 72 h post-dose for the assessment of serum calcium (Ca), serum intact parathyroid hormone (iPTH), and plasma cinacalcet concentrations.

Results

Overall, cinacalcet was well tolerated with no serious adverse events. Mean (standard deviation) percentage change in serum Ca over the first 12 h post-dose was ?2.93 % (5.70 %) with a nadir of ?4.34 % (6.04 %) at 8 h; Ca values returned to baseline by 48 h post-dose. Mean percentage change in iPTH over the first 12 h post-dose was 57.94 % (71.82 %) with a nadir of ?35.65 % (55.82 %) at 2 h. There was an inverse relationship between peak serum Ca concentration and body surface area (BSA) (r ²?=?0.41), although no relationship was found between area under the curve and age or BSA.

Conclusions

These data support future analysis to determine the therapeutic starting dose of cinacalcet for pediatric patients with sHPT on dialysis.     

Primary Hyperparathyroidism and Negative Tc99 Sestamibi Imaging: To Operate or Not?

Background

The indications for surgery in primary hyperparathyroidism (1HPT) are the same for patients with and without localization on imaging. However, patients with negative imaging may not be referred for surgery or the surgeon may be reluctant to operate. We compare outcomes in patients with negative imaging to those with localization.

Methods

A review of patients who underwent primary operation for 1HPT with a preoperative Tc99 sestamibi I-123 (MIBI) scan was conducted. Imaging, laboratory, operative findings, pathologic findings, and outcomes were used to compare patients with negative scans to those with localization.

Results

A total of 2,681 patients had an operation for 1HPT with preoperative MIBI. MIBI imaging was negative in 136 (5.7 %). The negative MIBI group had a lower calcium (10.9 vs. 11.0?mg/ml, P?=?0.02), phosphorus (2.9 vs. 3.1?mg/dl, P?P?=?0.02) and no difference in parathyroid hormone, 25-OH vitamin D, or bone loss. Multigland resection was higher with a negative scan (32 vs. 13 %, P?P?P?=?0.04) and parathyroid hormone (98 vs. 196?pg/ml, P?=?0.03) than those not cured. Patients with both a negative ultrasound result and negative MIBI had a cure rate of 89 %.

Conclusions

A curative operation is performed at an acceptably lower rate with negative MIBI imaging. A decision for surgery with a negative MIBI finding should consider lower cure rates and symptom severity.     

Renal calcium, phosphorus, magnesium and uric acid handling: comparison between stage III chronic kidney disease patients and healthy oldest old

Introduction

It is known that chronic kidney disease (CKD) and senescence bring about a progressive reduction in glomerular filtration rate (GFR) and that in the former this is usually associated with an increase in the fractional excretion of calcium, phosphorus, magnesium, and uric acid. However, it has not yet been explained how these substances are excreted in the healthy oldest old. Thus, in the present study, we examined the renal handling of these substances in very aged people in comparison with CKD patients with similar GFR levels (stage III??CKD).

Materials and methods

Twenty volunteers were studied; 10 of them were healthy very old (VO) (??75?years old) individuals and 10 were stage III CKD patients. Exclusion criteria were as follows: presence of altered (abnormally high or low) plasma calcium, phosphorus, magnesium and uric acid, as well as previous diagnoses of diabetes mellitus and obstructive uropathy and use of drugs that could alter plasma levels of the studied substances. All volunteers were on a diet with the same content of these elements (3-day dietary register). We measured calcium, phosphorus, magnesium, uric acid, creatinine in serum plasma and morning urine, as well as serum parathyroid hormone level, in each volunteer. From these data, fractional excretion (FE) of these substances was obtained. A statistical analysis was carried out using the Wilcoxon test.

Results

Serum creatinine: 1.8?±?0.4?mg/dl (CKD) versus 0.8?±?0.2?mg/dl (VO), p?=?0.0002; serum calcium: 9.1?±?0.3?mg/dl (CKD) versus 8.7?±?0.4 (VO), p?=?0.022; serum magnesium: 2.3?±?0.2?mg/dl (CKD) versus 2.0?±?0.1 (VO), p?=?0.05; serum phosphorus: 3.9?±?0.5?mg/dl (CKD) versus 3.0?±?0.4?mg/dl (VO), p?=?0.002; serum uric acid: 6.6?±?1.5 (CKD) versus 5.2?±?1.4?mg/dl (VO), p?=?0.04; FE of calcium: 2.5?±?1?% (CKD) versus 0.8?±?0.3?% (VO), p?=?0.04; FE of magnesium: 7.2?±?4.1?% (CKD) versus 2.9?±?0.9?% (VO), p?=?0.02; FE of phosphorus: 25?±?9?% (CKD) versus 9.1?±?5.7(VO), p?=?0.001; FE of uric acid: 10?±?3?% (CKD) versus 8?±?5?% (VO), p?=?0.05.

Conclusion

Serum levels and FE of calcium, phosphorus, magnesium and uric acid were significantly higher in CKD patients compared to healthy very old people with similar GFR, except for serum magnesium and FE of uric acid, which were similar in both groups.     

A naturally occurring rare analog of quercetin promotes peak bone mass achievement and exerts anabolic effect on osteoporotic bone

Summary

The effect of quercetin C-glucoside (QCG) on osteoblast function in vitro and bone formation in vivo was investigated. QCG supplementation promoted peak bone mass achievement in growing rats and new bone formation in osteopenic rats. QCG has substantial oral bioavailability. Findings suggest a significant bone anabolic effect of QCG.

Introduction

Recently, we showed that extracts of Ulmus wallichiana promoted peak bone mass achievement in growing rats and preserved trabecular bone mass and cortical bone strength in ovariectomized (OVx) rats. 3,3??,4??,5,7-Pentahydroxyflavone-6-C-??-d-glucopyranoside, a QCG, is the most abundant bioactive compound of U. wallichiana extract. We hypothesize that QCG exerts bone anabolic effects by stimulating osteoblast function.

Methods

Osteoblast cultures were harvested from rat calvaria and bone marrow (BM) to study differentiation and mineralization. In vivo, growing female Sprague Dawley rats and OVx rats with osteopenia were administered QCG (5.0 or 10.0?mg?kg^?1?day^?1) orally for 12?weeks. Efficacy was evaluated by examining changes in bone microarchitecture using histomorphometric and microcomputed tomographic analyses and by determination of new bone formation by fluorescent labeling of bone. Plasma and BM levels of QCG were determined by high-performance liquid chromatography.

Results

QCG was much more potent than quercetin (Q) in stimulating osteoblast differentiation, and the effect of QCG was not mediated by estrogen receptors. In growing rats, QCG increased BM osteoprogenitors, bone mineral density, bone formation rate, and cortical deposition. In osteopenic rats, QCG treatment increased bone formation rate and improved trabecular microarchitecture. Comparison with the sham group (ovary intact) revealed significant restoration of trabecular bone in osteopenic rats treated with QCG. QCG levels in the BM were ~50% of that of the plasma levels.

Conclusion

QCG stimulated modeling-directed bone accrual and exerted anabolic effects on osteopenic rats by direct stimulatory effect on osteoprogenitors likely due to substantial QCG delivery at tissue level following oral administration.     

Significant inverse relationship between serum undercarboxylated osteocalcin and glycemic control in maintenance hemodialysis patients

Summary

Increased levels of serum undercarboxylated osteocalcin, which were associated with bone metabolism markers, correlated inversely with indices of glucose metabolism (plasma glucose, hemoglobin A1C, and glycated albumin) in hemodialysis patients with abnormalities of bone metabolism.

Introduction

Undercarboxylated osteocalcin (ucOC), a possible marker of bone metabolism and one of the osteoblast-specific secreted proteins, has recently been reported to be associated with glucose metabolism. We tested the hypothesis that ucOC levels are associated with indices of glucose metabolism in chronic hemodialysis patients with abnormalities of bone metabolism.

Methods

Serum ucOC, bone alkaline phosphatase (BAP, a bone formation marker), and tartrate-resistant acid phosphatase-5b (TRACP-5b, a bone resorption marker) were measured in 189 maintenance hemodialysis patients (96 diabetics and 93 non-diabetics), and their relationships with glucose metabolism were examined.

Results

ucOC correlated positively with BAP (ρ?=?0.489, p?<?0.0001), TRACP-5b (ρ?=?0.585, p?<?0.0001) and intact parathyroid hormone (iPTH; ρ?=?0.621, p?<?0.0001). Serum ucOC levels in the diabetic patients were lower than those of non-diabetic patients (p?<?0.001), although there were no significant differences in serum BAP or TRACP-5b between diabetic and non-diabetic patients. Serum ucOC correlated negatively with plasma glucose (ρ?=??0.303, p?<?0.0001), hemoglobin A1C (ρ?=??0.214, p?<?0.01), and glycated albumin (ρ?=??0.271, p?<?0.001), although serum BAP or TRACP-5b did not. In multiple linear regression analysis, log [plasma glucose], log [hemoglobin A1C], and log [glycated albumin] were associated significantly with log [ucOC] after adjustment for age, gender, hemodialysis duration, and body mass index but were not associated with log [BAP], log [TRACP-5b], or log [intact PTH].

Conclusion

Increased levels of serum ucOC, which were associated with bone metabolism markers, were inversely associated with indices of glucose metabolism in hemodialysis patients.     

Obesity alters cortical and trabecular bone density and geometry in women

Summary

The goal in this study was to determine the relationship between body mass index and trabecular and cortical bone using quantitative computed tomography. A higher body mass index (BMI) was positively associated with trabecular and cortical bone parameters, and serum parathyroid hormone, and negatively associated with cortical volumetric bone mineral density (vBMD) and serum 25-hydroxy-vitamin D. When BMI is greater than 35 kg/m², adiposity affects vBMD and may explain the higher fracture risk in this population without low BMD.

Introduction

The influence of adult obesity on the trabecular and cortical bone, geometry, and strength has not been fully addressed. The goal in this study was to determine the relationship between body mass index and trabecular and cortical bone mass and geometry, over a wide range of body weights.

Methods

We examined 211 women (25–71 years; BMI 18–57 kg/m²) who were classified into three categories of BMI (kg/m²) including normal-weight (BMI?<?25), overweight and obese-class I (BMI 25–35) and obese-class II–III (BMI?>?35), and also by menopausal status. Volumetric bone mineral density (mg/cm³), trabecular, and cortical components as well as geometric characteristics at the 4%, 38%, and 66% from the distal tibia were measured by peripheral quantitative computed tomography, and serum was analyzed for parathyroid hormone (PTH) and 25-hydroxy-vitamin D (25OHD).

Results

Higher BMI was associated with greater values of trabecular bone and cortical BMC and area and PTH (r?>?0.39, p?<?0.001), but lower cortical vBMD and 25OHD (r?>??0.27, p?<?0.001). When controlling for lower leg muscle area, fat area was inversely associated with cortical vBMD (r?=??0.16, p?<?0.05). Premenopausal obese women with both higher BMI and PTH had lower cortical vBMD (r?<??0.40, p?<?0.001). While age is a predictor for most bone variables, fat mass explains more variance for vBMD, and lean mass and 25OHD explain greater variance in geometric and strength indices (p?<?0.05).

Conclusions

Severe obesity (BMI?>?35) increases trabecular vBMD and in the presence of a higher PTH is associated with a lower cortical vBMD without compromising bone geometry and strength. Whether or not a lower cortical vBMD in obesity influences fracture risk over time needs to be further explored.     

Comparative effects of teriparatide and ibandronate on spine bone mineral density (BMD) and microarchitecture (TBS) in postmenopausal women with osteoporosis: a 2-year open-label study

Summary

Treatment effects over 2 years of teriparatide vs. ibandronate in postmenopausal women with osteoporosis were compared using lumbar spine bone mineral density (BMD) and trabecular bone score (TBS). Teriparatide induced larger increases in BMD and TBS compared to ibandronate, suggesting a more pronounced effect on bone microarchitecture of the bone anabolic drug.

Introduction

The trabecular bone score (TBS) is an index of bone microarchitecture, independent of bone mineral density (BMD), calculated from anteroposterior spine dual X-ray absorptiometry (DXA) scans. The potential role of TBS for monitoring treatment response with bone-active substances is not established. The aim of this study was to compare the effects of recombinant human 1–34 parathyroid hormone (teriparatide) and the bisphosphonate ibandronate (IBN), on lumbar spine (LS) BMD and TBS in postmenopausal women with osteoporosis.

Methods

Two patient groups with matched age, body mass index (BMI), and baseline LS BMD, treated with either daily subcutaneous teriparatide (N?=?65) or quarterly intravenous IBN (N?=?122) during 2 years and with available LS BMD measurements at baseline and 2 years after treatment initiation were compared.

Results

Baseline characteristics (overall mean ± SD) were similar between groups in terms of age 67.9?±?7.4 years, body mass index 23.8?±?3.8 kg/m², BMD L1–L4 0.741?±?0.100 g/cm², and TBS 1.208?±?0.100. Over 24 months, teriparatide induced a significantly larger increase in LS BMD and TBS than IBN (+7.6 %?±?6.3 vs. +2.9 %?±?3.3 and +4.3 %?±?6.6 vs. +0.3 %?±?4.1, respectively; P?<?0.0001 for both). LS BMD and TBS were only weakly correlated at baseline (r ²?=?0.04) with no correlation between the changes in BMD and TBS over 24 months.

Conclusions

In postmenopausal women with osteoporosis, a 2-year treatment with teriparatide led to a significantly larger increase in LS BMD and TBS than IBN, suggesting that teriparatide had more pronounced effects on bone microarchitecture than IBN.     

Defining physiologically “normal” vitamin D in African Americans

Summary

The relationship between serum 25(OH)D and intact parathyroid hormone (iPTH) was evaluated in the Multicenter Osteoarthritis Study (MOST). No further change in iPTH was observed for African Americans with 25(OH)D levels above 20?ng/ml, suggesting that compared to Caucasians, lower vitamin D targets for sufficiency may be appropriate for African Americans.

Introduction

Vitamin D levels ≥30?ng/ml are commonly considered “normal” based upon maximal suppression of iPTH; however, this has recently been challenged and the optimal 25(OH)D level among non-Caucasians is unclear. We evaluated the cross-sectional relationship between serum 25(OH)D and iPTH in a sample of Caucasian and African American adults.

Methods

We used baseline serum samples of participants from the Multicenter Osteoarthritis Study (MOST) for this analysis and used three methods to model the relationship between 25(OH)D and iPTH: ordinary least squares regression (OLS), segmented regression and Helmert contrasts.

Results

Among Caucasians (n?=?1,258), 25(OH)D and iPTH ranged from 4 to 51?ng/ml and 2 to 120?pg/ml and from 3 to 32?ng/ml and 3 to 119?pg/ml in African Americans (n?=?423). We observed different thresholds between African Americans and Caucasians using each analytic technique. Using 25(OH)D as a categorical variable in OLS, iPTH was statistically higher at lower 25(OH)D categories than the 24–32?ng/ml referent group among Caucasians. However, in African Americans, the mean iPTH was only significantly higher at 25(OH)D levels below 15?ng/ml. Using segmented regression, iPTH appeared to stabilize at a lower 25(OH)D level in African Americans (19–23?ng/ml) compared to in Caucasians (>32?ng/ml). Helmert contrasts also revealed a lower threshold in African Americans than Caucasians.

Conclusion

Among MOST participants, the 25(OH)D thresholds at which no further change in iPTH was observed was approximately 20?ng/ml in African Americans versus approximately 30?ng/ml in Caucasians, suggesting optimal vitamin D levels in Caucasians may not be applicable to African Americans.     

Bone mass and vitamin D levels in women with a diagnosis of fibromyalgia

Summary

No differences in either bone mineral density or serum 25OHD levels have been found between 205 women with fibromyalgia (both pre- and postmenopausal) and their controls. However, a lack of the expected 25OHD summer rise was observed in patients.

Introduction

Contradictory data have been published regarding a possible association between fibromyalgia and osteoporosis or hypovitaminosis D. Most studies, however, have been performed in small size samples and have excluded postmenopausal women. We decided to study this association in a larger sample of fibromyalgia patients including both pre- and postmenopausal women.

Methods

Two hundred five patients were recruited from a clinic specializing in fibromyalgia and 205 healthy controls were enrolled from the census of a Primary Care Center. Controls were matched with patients by age and the time of the year they were included in the study. Bone mineral density (BMD) was measured by DXA. Serum 25OHD, iPTH, P1NP, and CTX were also determined.

Results

BMD was similar in both groups (lumbar spine, 0.971?±?0.146 g/cm² in patients and 0.970?±?0.132 g/cm² in controls; femoral neck, 0.780?±?0.122 g/cm² and 0.785?±?0.117 g/cm², respectively). 25OHD levels were also similar: 23.0?±?9.5 ng/ml and 24.1?±?9.6 ng/ml. However, while controls showed the usual summer rise in 25OHD, fibromyalgia patients did not. PTH did not show seasonal changes, but on average was higher in patients (51 pg/ml vs. 48 pg/ml; p?=?0.034). P1NP or CTX were similar in both groups.

Conclusions

No differences in BMD were found between patients and controls. As for 25OHD, a lack of its expected summer rise was observed. It is doubtful whether this has any homeostatic consequence. We consider that the association reported in other studies is merely circumstantial, and not due to the intrinsic characteristics of these disorders.     

Classification of Parathyroid Cancer

Purpose

Parathyroid cancer is rare and often has a poor outcome. There is no classification system that permits prediction of outcome in patients with parathyroid cancer. This study was designed to validate two prognostic classification systems developed by Talat and Schulte in 2010 (??Clinical Presentation, Staging and Long-term Evolution of Parathyroid Cancer,?? Ann Surg Oncol 2010;17:2156?C74) derived from a retrospective literature review of 330 patients.

Methods

This study contains 82 formerly unreported patients with parathyroid cancer. Death due to disease was the primary end point, and recurrence and disease-free survival were the secondary end points. Data acquisition used a questionnaire of predefined criteria. Low risk was defined by capsular and soft tissue invasion alone; high risk was defined by vascular or organ invasion, and/or lymph node or distant metastasis. A differentiated classification system further classified high-risk cancer into vascular invasion alone (class II), lymph node metastasis or organ invasion (class III), and distant metastasis (class IV). Statistical analyses included risk analysis, Kaplan-Meier analysis, and receiver?Coperating characteristic (ROC) analysis.

Results

Follow-up ranged 2?C347?months (mean 76?months). Mortality was exclusive to the high- risk group, which also predicted a significant risk of recurrence (risk ratio 9.6; 95% confidence interval 2.4?C38.4; P?2?=?8.7; P?n?=?45). The differentiated classification also provided a good prognostic model with an area under the ROC curve of 0.83 in ROC analysis, with significant impairment of survival between classes (98.6%, 79.2%, 71.4%, 40.0%, P?Conclusions This study confirms the validity of both classification systems for disease outcome in patients with parathyroid cancer.     

Replication study of candidate genes/loci associated with osteoporosis based on genome-wide screening

Summary

Osteoporosis is a major public health problem characterized by low bone mineral density (BMD). This replication study confirmed 38 single-nucleotide polymorphisms (SNPs) out of 139 SNPs previously reported in three recent genome-wide association studies (GWASs) in an independent US white sample. Ten SNPs achieved combined p?<?3.6?×?10^?4.

Introduction

BMD is under strong genetic control. This study aims to verify the potential associations between BMD and candidate genes/loci reported by GWAS of FHS100K, Icelandic deCODE, and UK-NL.

Methods

Eight promising (at the genome-wide significant level after Bonferroni correction) and 131 available sub-promising (at the most stringent p value, p?<?5.5?×?10^?5 in the three GWASs reports) SNPs were selected. By using genotypic information from Affymetrix 500 K SNP arrays, we tested their associations with BMD in 1,000 unrelated US whites. Fisher's combined probability method was used to quantify the overall evidence of association. BMD was measured by dual energy X-ray absorptiometry.

Results

Two promising SNPs, rs3762397 and rs3736228, were replicated in the current study with p?<?0.05. Besides, 36 sub-promising SNPs were replicated at the same significant level. Ten SNPs achieved significant combined p?<?3.6?×?10^?4 (0.05/139 SNPs, corrected for multiple testing).

Conclusions

Osteoporosis susceptibility of 38 SNPs was replicated in 1,000 unrelated US whites. This study showed promise for replication of some initial genome-wide association signals.     

Conversion from conventional in-centre thrice-weekly haemodialysis to short daily home haemodialysis ameliorates uremia-associated clinical parameters

Background

Under physiological conditions, kidneys work continuously, 168?h/week. In contrast, patients with end-stage renal disease are usually dialysed only 12?h/week. Even if considered adequate by current Kt/V-based dose estimates, this unphysiological dose is associated with an unacceptable annual mortality rate of 10?C20%. Increasing dialysis dose might ameliorate this mortality rate.

Design

Eleven patients were switched from their conventional haemodialysis (cHD, 3?×?4?h/week) to an intensified short daily home haemodialysis regimen (sdhHD, 6?×?3?h/week) and followed up for 12?months. Different parameters were evaluated before treatment conversion and quarterly during follow-up [i.e. dialysis efficacy, mean arterial pressure (MAP), antihypertensive drug score, haemoglobin, transferrin saturation, ferritin, dose of erythropoiesis-stimulating agents (ESA), iron requirement, parameters of nutrition (body weight, albumin, protein), C-reactive protein, calcium?Cphosphate product, alkaline phosphatase (AP), intact parathyroid hormone (iPTH) and amount of phosphate-binding pharmacotherapy].

Results

HD efficacy as assessed by cumulative blood volume increased after dialysis intensification (P?<?0.01). The pre- and post-dialytic MAP declined during the study period (P?<?0.0001), while antihypertensive drugs could be reduced (P?=?0.02). Haemoglobin levels improved (P?<?0.0001). Additionally, the need for ESAs fell under intensified sdhHD (P?=?0.008). Nutritional status improved [albumin, P?=?0.03; total serum protein, P?=?0.02; ??dry?? body weight (BW) and body mass index (BMI) (both P?<?0.001)]. The calcium?Cphosphate product declined (P?<?0.01), without changes in the dose of phosphate binders.

Conclusion

Conversion from conventional in-centre to short daily home HD leads to an improvement in numerous dialysis-associated metabolic variables and thus represents an attractive treatment modality for selected patients.