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T L Nickolas,
E M Stein,
E Dworakowski,
K K Nishiyama,
M Komandah-Kosseh,
C A Zhang,
D J McMahon,
X S Liu,
S Boutroy,
S Cremers, E Shane
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ABSTRACT: Chronic kidney disease (CKD) patients may have high rates of bone loss and fractures, but microarchitectural and biochemical mechanisms of bone loss in CKD patients have not been fully described. In this longitudinal study of 53 patients with CKD Stages 2-5D, we used dual energy X-ray absorptiometry (DXA), high resolution peripheral quantitative computed tomography (HRpQCT) and biochemical markers of bone metabolism to elucidate effects of CKD on the skeleton. Median follow-up was 1.5 years (Range 0.9 to 4.3 years); bone changes were annualized and compared to baseline. By DXA, there were significant declines in areal bone mineral density (BMD) of the total hip and ultradistal radius: -1.3% (95% CI: -2.1 to -0.6) and -2.4% (95% CI: -4.0 to -0.9), respectively. By HRpQCT at the distal radius, there were significant declines in cortical area, density and thickness, and increases in porosity: -2.9% (95% CI -3.7 to -2.2), -1.3% (95% CI -1.6 to -0.6), -2.8% (95% CI -3.6 to -1.9), and +4.2% (95% CI 2.0 to 6.4) respectively. Radius trabecular area increased significantly: +0.4% (95% CI 0.2 to 0.6), without significant changes in trabecular density or microarchitecture. Elevated time-averaged levels of parathyroid hormone (PTH) and bone turnover markers predicted cortical deterioration. Higher levels of serum 25-hydroxyvitamin D predicted decreases in trabecular network heterogeneity. These data suggest that significant cortical loss occurs with CKD, which is mediated by hyperparathyroidism and elevated turnover. Future investigations are required to determine whether these cortical losses can be attenuated by treatments that reduce PTH levels and remodeling rates. © 2013 American Society for Bone and Mineral Research.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 03/2013; · 6.04 Impact Factor
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Bm Misof,
S Gamsjaeger,
A Cohen,
B Hofstetter,
P Roschger,
E Stein,
Tl Nickolas,
Hf Rogers,
D Dempster,
H Zhou,
R Recker,
J Lappe,
D McMahon,
Ep Paschalis,
P Fratzl, E Shane,
K Klaushofer
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ABSTRACT: Idiopathic osteoporosis (IOP) in premenopausal women is characterized by fragility fractures at low or normal bone mineral density (BMD) in otherwise healthy women with normal gonadal function. Histomorphometric analysis of transiliac bone biopsy samples has revealed microarchitectural deterioration of cancellous bone and thinner cortices. To examine bone material quality, we measured the bone mineralization density distribution (BMDD) in biopsy samples by quantitative backscattered electron imaging (qBEI), and mineral/matrix ratio, mineral crystallinity/maturity, relative proteoglycan content and collagen cross-link ratio at actively bone forming trabecular surfaces by Raman and Fourier Transform Infrared (FTIRM) microspectroscopic techniques. The study groups included: premenopausal women with idiopathic fractures (IOP, n = 45), or idiopathic low BMD (Z-score ≤-2.0 at spine and/or hip) but no fractures (ILBMD, n = 19), and healthy controls (CONTROL, n = 38). BMDD of cancellous bone showed slightly lower mineral content in IOP (both Cn.CaMean and Cn.CaPeak are 1.4% lower) and in ILBMD (both are 1.6% lower, p < 0.05) versus CONTROL, but no difference between IOP and ILBMD. Similar differences were found when affected groups were combined versus CONTROL. The differences remained significant after adjustment for mineralizing surface (MS/BS), suggesting that the reduced mineralization of bone matrix cannot be completely accounted for by differences in bone turnover. Raman and FTIRM analysis at forming bone surfaces showed no differences between combined IOP/ILBMD groups versus CONTROL, with the exceptions of increased proteoglycan content per mineral content and increased collagen cross-link ratio. When the two affected subgroups were considered individually, mineral/matrix ratio and collagen cross-link ratio were higher in IOP than ILBMD. In conclusion, our findings suggest that bone material properties differ between premenopausal women with IOP/ILBMD and normal controls. In particular, the altered collagen properties at sites of active bone formation support the hypothesis that affected women have osteoblast dysfunction that may play a role in bone fragility. © 2012 American Society for Bone and Mineral Research.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 07/2012; · 6.04 Impact Factor
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L. E. Nikkel,
S. Mohan,
A. Zhang,
D. J. McMahon,
S. Boutroy,
G. Dube,
B. Tanriover,
D. Cohen,
L. Ratner,
C. S. Hollenbeak,
M. B. Leonard, E. Shane,
T. L. Nickolas
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ABSTRACT: Corticosteroid use after kidney transplantation results in severe bone loss and high fracture risk. Although corticosteroid withdrawal in the early posttransplant period has been associated with bone mass preservation, there are no published data regarding corticosteroid withdrawal and risk of fracture. We hypothesized lower fracture incidence in patients discharged from the hospital without than with corticosteroids after transplantation. From the United States Renal Data System (USRDS), 77, 430 patients were identified who received their first kidney transplant from 2000 to 2006. Fracture incidence leading to hospitalization was determined from 2000 to 2007; discharge immunosuppression was determined from United Networks for Organ Sharing forms. Time-to-event analyses were used to evaluate fracture risk. Median (interquartile range) follow-up was 1448 (808-2061) days. There were 2395 fractures during follow-up; fracture incidence rates were 0.008 and 0.0058 per patient-year for recipients discharged with and without corticosteroid, respectively. Corticosteroid withdrawal was associated with a 31% fracture risk reduction (HR 0.69; 95% CI 0.59-0.81). Fractures associated with hospitalization are significantly lower with regimens that withdraw corticosteroid. As this study likely underestimates overall fracture incidence, prospective studies are needed to determine differences in overall fracture risk in patients managed with and without corticosteroids after kidney transplantation.
American Journal of Transplantation 12/2011; 12(3):649-59. · 6.39 Impact Factor
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Mishaela R Rubin,
David W Dempster,
James Sliney,
Hua Zhou,
Thomas L Nickolas,
Emily M Stein,
Elzbieta Dworakowski,
Maryann Dellabadia,
Rebecca Ives,
Donald J McMahon,
Chiyuan Zhang,
Shonni J Silverberg, Elizabeth Shane,
Serge Cremers,
John P Bilezikian
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ABSTRACT: Hypoparathyroidism is associated with abnormal structural and dynamic skeletal properties. We hypothesized that parathyroid hormone(1-84) [PTH(1-84)] treatment would restore skeletal properties toward normal in hypoparathyroidism. Sixty-four subjects with hypoparathyroidism were treated with PTH(1-84) for 2 years. All subjects underwent histomorphometric assessment with percutaneous iliac crest bone biopsies. Biopsies were performed at baseline and at 1 or 2 years. Another group of subjects had a single biopsy at 3 months, having received tetracycline before beginning PTH(1-84) and prior to the biopsy (quadruple-label protocol). Measurement of biochemical bone turnover markers was performed. Structural changes after PTH(1-84) included reduced trabecular width (144 ± 34 µm to 128 ± 34 µm, p = 0.03) and increases in trabecular number (1.74 ± 0.34/mm to 2.07 ± 0.50/mm, p = 0.02) at 2 years. Cortical porosity increased at 2 years (7.4% ± 3.2% to 9.2% ± 2.4%, p = 0.03). Histomorphometrically measured dynamic parameters, including mineralizing surface, increased significantly at 3 months, peaking at 1 year (0.7% ± 0.6% to 7.1% ± 6.0%, p = 0.001) and persisting at 2 years. Biochemical measurements of bone turnover increased significantly, peaking at 5 to 9 months of therapy and persisting for 24 months. It is concluded that PTH(1-84) treatment of hypoparathyroidism is associated with increases in histomorphometric and biochemical indices of skeletal dynamics. Structural changes are consistent with an increased remodeling rate in both trabecular and cortical compartments with tunneling resorption in the former. These changes suggest that PTH(1-84) improves abnormal skeletal properties in hypoparathyroidism and restores bone metabolism toward normal euparathyroid levels.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 07/2011; 26(11):2727-36. · 6.04 Impact Factor
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ABSTRACT: Ritonavir (RTV) is a commonly used antiretroviral associated with bone loss. We show that peripheral blood mononuclear cells (PBMCs) from human immunodeficiency virus (HIV)-positive women on RTV are more likely to differentiate into osteoclast-like cells when cultured with their own sera than PBMCs and sera from HIV- women or HIV+ on other antiretrovirals.
RTV increases differentiation of human adherent PBMCs to functional osteoclasts in vitro, and antiretroviral regimens containing RTV have been associated with low bone mineral density (BMD) and bone loss.
BMD, proresorptive cytokines, bone turnover markers (BTMs), and induction of osteoclast-like cells from adherent PBMCs incubated either with macrophage colony-stimulating factor (MCSF) and receptor activator of nuclear factor κB ligand (RANKL) or with autologous serum were compared in 51 HIV- and 68 HIV+ postmenopausal women.
BMD was lower, and serum proresorptive cytokines and BTMs were higher in HIV+ versus HIV- women. Differentiation of osteoclast-like cells from adherent PBMCs exposed to either MCSF/RANKL or autologous serum was greater in HIV+ women. Induction of osteoclast-like cells was greater from PBMCs exposed to autologous sera from HIV+ women on RTV-containing versus other regimens (172 ± 14% versus 110 ± 10%, p < 0.001). Serum-based induction of osteoclast-like cells from adherent PBMCs correlated with certain BTMs but not BMD.
HIV infection and antiretroviral therapy are associated with higher BTMs and increased differentiation of osteoclast-like cells from adherent PBMCs, especially in women on regimens containing RTV. HIV+ postmenopausal women receiving RTV may be at greater risk for bone loss.
Osteoporosis International 05/2011; 22(5):1459-68. · 4.58 Impact Factor
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A Cohen,
R R Recker,
J Lappe,
D W Dempster,
S Cremers,
D J McMahon,
E M Stein,
J Fleischer,
C J Rosen,
H Rogers,
R B Staron,
J Lemaster, E Shane
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ABSTRACT: In men, idiopathic osteoporosis (IOP) is often associated with low serum insulin-like growth factor (IGF-1) and reduced bone formation. The characteristics of premenopausal women with IOP are not well defined. We aimed to define the clinical, reproductive, and biochemical characteristics of premenopausal women with unexplained osteoporosis.
This is a cross-sectional study of 64 women with unexplained osteoporosis, 45 with fragility fractures, 19 with low bone mineral density (BMD; Z-score less than or equal to -2.0) and 40 normal controls. The following are the main outcome measures: clinical and anthropometric characteristics, reproductive history, BMD, gonadal and calciotropic hormones, IGF-1, and bone turnover markers (BTMs).
Subjects had lower BMI and BMD than controls, but serum and urinary calcium, serum estradiol, vitamin D metabolites, IGF-1, and most BTMs were similar. Serum parathyroid hormone (PTH) and the resorption marker, tartrate-resistant acid phosphatase (TRAP5b), were significantly higher in both groups of subjects than controls and directly associated in all groups. Serum IGF-1 and all BTMs were directly associated in controls, but the association was not significant after controlling for age. There was no relationship between serum IGF-1 and BTMs in subjects. There were few differences between women with fractures and low BMD.
Higher serum TRAP5b and PTH suggest that increased bone turnover, possibly related to subclinical secondary hyperparathyroidism could contribute to the pathogenesis of IOP. The absence of differences between women with fractures and those with very low BMD indicates that this distinction may not be clinically useful to categorize young women with osteoporosis.
Osteoporosis International 03/2011; 23(1):171-82. · 4.58 Impact Factor
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ABSTRACT: We evaluated vitamin D status in HIV+ and HIV- postmenopausal African-American (AA) and Hispanic women. Most women (74-78%) had insufficient 25-hydroxyvitamin D (25OHD) levels, regardless of HIV status. 25OHD was lower in AA women and women lacking supplement use, providing support for screening and supplementation. Among HIV+ women, 25OHD was associated with current CD4 but not type of antiretroviral therapy.
To evaluate vitamin D status and factors associated with vitamin D deficiency and insufficiency in HIV-infected (HIV+) postmenopausal minority women.
In this cross-sectional study, 89 HIV+ and 95 HIV- postmenopausal women (33% AA and 67% Hispanic) underwent assessment of 25OHD, 1,25-dihydroxyvitamin D, parathyroid hormone, markers of bone turnover and bone mineral density by dual energy X-ray absorptiometry.
The prevalence of low 25OHD did not differ by HIV status; the majority of both HIV+ and HIV- women (74-78%) had insufficient levels (<30 ng/ml). Regardless of HIV status, 25OHD was significantly lower in AA subjects, and higher in subjects who used both calcium and multivitamins. In HIV+ women on antiretroviral therapy (ART), 25OHD was directly associated with current CD4 count (r=0.32; p<0.01) independent of age, ethnicity, BMI, or history of AIDS-defining illness. No association was observed between 1,25(OH)(2)D and CD4 count or between serum 25OHD, 1,25(OH)(2)D or PTH and type of ART.
In postmenopausal minority women, vitamin D deficiency was highly prevalent and associated with AA race and lack of supplement use, as well as lower current CD4 cell count. These results provide support for screening and repletion of vitamin D in HIV+ patients.
Osteoporosis International 02/2011; 22(2):477-87. · 4.58 Impact Factor
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ABSTRACT: Vitamin D deficiency is prevalent among patients with end-stage organ failure awaiting transplant. Low serum 25-hydroxyvitamin D (25-OHD) levels in these patients may be related to many disease-specific factors, as well as decreased sunlight exposure and limited intake of foods containing vitamin D. Low serum 25-OHD levels are also extremely common following solid organ transplantation, both during the immediate postoperative period and in long-term graft recipients. Demographic and lifestyle factors are important in determining D status in transplant recipients. Worse vitamin D status is associated with poorer general health, lower albumin, and even decreased survival among these patients. Although several studies have demonstrated that active forms of vitamin D and its analogues prevent bone loss following transplantation, the data do not show consistent benefit. These therapies may have particular utility after renal transplantation. However, given the narrow therapeutic window with respect to hypercalcemia and hypercalciuria, and the demonstrated efficacy of bisphosphonates to prevent post-transplantation bone loss, we regard these agents as adjunctive rather than primary therapy for transplantation osteoporosis. The effects of 1,25(OH)(2)D on the immune system, which are still being elucidated, may have potential for reducing infections and preventing allograft rejection after transplantation.
Osteoporosis International 01/2011; 22(7):2107-18. · 4.58 Impact Factor
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M R Rubin,
J S Manavalan,
D W Dempster,
J Shah,
S Cremers,
S Kousteni,
H Zhou,
D J McMahon,
A Kode,
J Sliney, E Shane,
S J Silverberg,
J P Bilezikian
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ABSTRACT: The osteoanabolic properties of PTH may be due to increases in the number and maturity of circulating osteogenic cells. Hypoparathyroidism is a useful clinical model because this hypothesis can be tested by administering PTH.
The objective of the study was to characterize circulating osteogenic cells in hypoparathyroid subjects during 12 months of PTH (1-84) administration.
Osteogenic cells were characterized using flow cytometry and antibodies against osteocalcin, an osteoblast-specific protein product, and stem cell markers CD34 and CD146. Changes in bone formation from biochemical markers and quadruple-labeled transiliac crest bone biopsies (0 and 3 month time points) were correlated with measurements of circulating osteogenic cells.
The study was conducted at a clinical research center.
Nineteen control and 19 hypoparathyroid patients were included in the study.
Intervention included the administration of PTH (1-84).
Osteocalcin-positive cells were lower in hypoparathyroid subjects than controls (0.7 ± 0.1 vs. 2.0 ± 0.1%; P < 0.0001), with greater coexpression of the early cell markers CD34 and CD146 among the osteocalcin-positive cells in the hypoparathyroid subjects (11.0 ± 1.0 vs. 5.6 ± 0.7%; P < 0.001). With PTH (1-84) administration, the number of osteogenic cells increased 3-fold (P < 0.0001), whereas the coexpression of the early cell markers CD34 and CD146 decreased. Increases in osteogenic cells correlated with circulating and histomorphometric indices of osteoblast function: N-terminal propeptide of type I procollagen (R(2) = 0.4, P ≤ 0.001), bone-specific alkaline phosphatase (R(2) = 0.3, P < 0.001), osteocalcin (R(2) = 0.4, P < 0.001), mineralized perimeter (R(2) = 0.5, P < 0.001), mineral apposition rate (R(2) = 0.4, P = 0.003), and bone formation rate (R(2) = 0.5, P < 0.001).
It is likely that PTH stimulates bone formation by stimulating osteoblast development and maturation. Correlations between circulating osteogenic cells and histomorphometric indices of bone formation establish that osteoblast activity is being identified by this methodology.
The Journal of clinical endocrinology and metabolism 09/2010; 96(1):176-86. · 6.50 Impact Factor
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ABSTRACT: High-resolution peripheral quantitative computed tomography (HR-pQCT) is a promising in vivo imaging technique that can be used to assess the three-dimensional microstructure of the radius and tibia. Micro finite element models can also be constructed from these images to estimate the mechanical competence of these sites, giving this technique the potential in the clinical diagnosis of osteoporosis. However, the mechanical properties of the peripheral sites may not be predictive of the properties at the central sites. Image-based finite element analysis was performed on sixty-nine premenopausal women, 12 with idiopathic osteoporosis and 57 normal controls, who underwent HR-pQCT scans of the distal radius and distal tibia and central quantitative computed tomography scans of the proximal femur and lumbar spine. Significant correlations were found between the stiffness of the two peripheral sites (r=0.86), the two central sites (r=0.49) and also between the peripheral and central skeletal sites (r=0.56-0.70).
Bioengineering Conference, Proceedings of the 2010 IEEE 36th Annual Northeast; 04/2010
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A Cohen,
D W Dempster,
R Müller,
X E Guo,
T L Nickolas,
X S Liu,
X H Zhang,
A J Wirth,
G H van Lenthe,
T Kohler,
D J McMahon,
H Zhou,
M R Rubin,
J P Bilezikian,
J M Lappe,
R R Recker, E Shane
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ABSTRACT: We compared microarchitecture and mechanical competence parameters measured by high-resolution peripheral quantitative computed tomography (HR-pQCT) and finite-element analysis of radius and tibia to those measured by histomorphometry, micro-CT, and finite-element analysis of transiliac bone biopsies. Correlations were weak to moderate between parameters measured on biopsies and scans.
HR-pQCT is a new imaging technique that assesses trabecular and cortical bone microarchitecture of the radius and tibia in vivo. The purpose of this study was to determine the extent to which microarchitectural variables measured by HR-pQCT reflect those measured by the "gold standard," transiliac bone biopsy.
HR-pQCT scans (Xtreme CT, Scanco Medical AG) and iliac crest bone biopsies were performed in 54 subjects (aged 39 +/- 10 years). Biopsies were analyzed by 2D quantitative histomorphometry and 3D microcomputed tomography (microCT). Apparent Young's modulus, an estimate of mechanical competence or strength, was determined by micro-finite-element analysis (microFE) of biopsy microCT and HR-pQCT images.
The strongest correlations observed were between trabecular parameters (bone volume fraction, number, separation) measured by microCT of biopsies and HR-pQCT of the radius (R 0.365-0.522; P < 0.01). Cortical width of biopsies correlated with cortical thickness by HR-pQCT, but only at the tibia (R = 0.360, P < 0.01). Apparent Young's modulus calculated by microFE of biopsies correlated with that calculated for both radius (R = 0.442; P < 0.001) and tibia (R = 0.380; P < 0.001) HR-pQCT scans.
The associations between peripheral (HR-pQCT) and axial (transiliac biopsy) measures of microarchitecture and estimated mechanical competence are significant but modest.
Osteoporosis International 06/2009; 21(2):263-73. · 4.58 Impact Factor
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E. Seeman,
T. Thomas,
S. K. Boyd,
S. Boutroy, E. Shane,
D. A. Hanley,
C. Bogado,
A. M. Cheung,
S. Majumdar,
D. Sellmeyer,
A. Kearns,
P. D. Delmas
Bone 01/2009; 44. · 4.02 Impact Factor
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ABSTRACT: Antiepileptic drugs (AEDs) may have adverse effects on bone mineral density (BMD) and metabolism. We previously reported biochemical evidence of increased bone turnover in premenopausal women with epilepsy on phenytoin monotherapy compared with those on carbamazepine, lamotrigine, and valproate. We therefore hypothesized that rates of bone loss would be higher in young women treated with phenytoin.
Ninety-three premenopausal women with epilepsy receiving a single AED (carbamazepine, lamotrigine, phenytoin, or valproate) participated. Subjects completed nutritional and physical activity questionnaires. Biochemical indices of bone and mineral metabolism and BMD of the proximal femur and lumbar spine were measured at baseline and 1 year.
Participants reported high calcium intake (>1,000 mg/day) and were physically active. Significant loss (2.6%) was seen at the femoral neck in the phenytoin group. BMD remained stable in the other AED groups. Bone turnover markers and calciotropic hormones were unchanged after 1 year in all groups except for a significant decline in urine N-telopeptide in the phenytoin group. In women receiving phenytoin, lower serum 25-hydroxyvitamin D concentrations were associated with higher parathyroid hormone, bone alkaline phosphatase, and urine N-telopeptide levels, a biochemical pattern consistent with secondary hyperparathyroidism and increased remodeling.
In this study, young women treated with phenytoin had significant femoral neck bone loss over 1 year. In contrast, those treated with carbamazepine, lamotrigine, and valproate did not have detectable adverse effects on bone turnover or bone mineral density. These results raise concerns about the long-term effects of phenytoin monotherapy on bone in young women with epilepsy.
Neurology 05/2008; 70(18):1586-93. · 8.31 Impact Factor
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ABSTRACT: By conventional 2-dimensional, histomorphometric analysis, we and others have previously shown that cancellous bone architecture is preserved in mild primary hyperparathyroidism (PHPT). We have now extended these observations to a 3-dimensional analysis using microcomputed tomography (microCT). Iliac crest bone biopsies were analyzed from the following subjects with PHPT: 22 postmenopausal women; 7 premenopausal women; similar numbers of normal pre- and postmenopausal women served as controls. Fifteen men with PHPT were also studied. Postmenopausal women with PHPT demonstrated features of preserved cancellous bone as shown by smaller age-related declines in cancellous bone volume (BV/TV) and connectivity density (Conn.D) and no change in bone surface/total volume (BS/TV) as compared to normal women. In postmenopausal women with PHPT, cancellous bone volume (BV/TV), bone surface/total volume, and connectivity density (Conn.D) were all higher, and trabecular separation (Tb.Sp) was lower than in postmenopausal controls. In sharp contrast to the findings in normal women, no structural variables in PHPT women were correlated with age. Also of note, there was no difference in any 3-dimensional index between women and men with PHPT. We conclude that three-dimensional, cancellous bone microarchitecture is preserved in patients with mild primary hyperparathyroidism.
Bone 08/2007; 41(1):19-24. · 4.02 Impact Factor
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Journal of Bone and Mineral Research. 01/2005; 20(9):S45-S45.
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E Shane
Journal of Clinical Endocrinology & Metabolism 03/2001; 86(2):485-93. · 6.50 Impact Factor
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ABSTRACT: Osteoporosis, common in European and South American adults with celiac disease, has not been reported in those patients with celiac disease residing in North America. We therefore evaluated bone density in a group of patients from the United States.
Patients (105 women and 23 men) with celiac disease, who had completed a questionnaire and had bone mineral density (BMD) measured by dual energy x-ray absorptiometry, were evaluated. The patients were an average age of 56 yr old (range 21-83 yr) and had been on a gluten-free diet from 0 months to 46 yr (mean 7.5 yr).
Osteoporosis (T score < -2.5) was present in 34% of the patients at the lumbar spine, 27% at the femoral neck, and 36% at the radius. Low bone mass (T score between -1.0 and -2.5) was present in 38% at the lumbar spine, 44% at the femoral neck, and 32% at the radius. When compared to age-matched controls, men were more severely affected than women. BMD did not differ between those on a gluten-free diet and those who had not begun therapy. BMD was remeasured 16 +/- 2 months after beginning a gluten-free diet in 5 patients; it increased by 7.5% at the femoral neck (p < 0.02). In 16 patients who had followed a gluten-free diet for an average of 12 yr, BMD remained stable over an additional 2 yr of observation.
Osteoporosis and low bone mass often affect North American adults with celiac disease, whether or not they are on dietary therapy. Routine screening for osteoporosis is indicated in patients with celiac disease.
The American Journal of Gastroenterology 01/2001; 96(1):112-9. · 7.28 Impact Factor
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ABSTRACT: Endoscopy provides an opportunity to diagnose unsuspected celiac disease.
We prospectively identified patients undergoing endoscopy for reasons other than the evaluation of diarrhea or suspected malabsorption, who had endoscopic signs in the duodenum suggestive of celiac disease and in whom villous atrophy was confirmed. Patients were assessed for nutritional deficiencies, reduced bone density, parameters of calcium metabolism, and malignancies.
Nine patients (3 women and 6 men) were identified among 1749 patients undergoing endoscopy between January 1990 and May 1998, representing a rate of unsuspected celiac disease of 1 per 194 endoscopies. The duodenal abnormalities were as follows: reduced or absent folds in 6, scalloped folds in 5, mosaic appearance in 3, and mucosal fissures in 2. Assessment revealed iron deficiency in 5, folate deficiency in 1, osteopenia in 4, osteoporosis in 1, and hypocalciuria in 4. Three had malignancies associated with celiac disease, 2 esophageal squamous carcinomas, and 1 jejunal adenocarcinoma.
Unsuspected celiac disease can be diagnosed at endoscopy by recognition of changes in the duodenum. When detected, patients have one or more manifestations of the disease. Celiac disease is more common in the United States than previously considered and endoscopy provides an opportunity to establish the diagnosis.
Gastrointestinal Endoscopy 02/2000; 51(1):60-5. · 4.88 Impact Factor
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ABSTRACT: Differences in the prevalence of vitamin D deficiency may explain why the frequency of symptoms in patients with primary hyperparathyroidism varies geographically. This study was performed to determine the prevalence in the United States of low 25-hydroxyvitamin D levels among patients with mild primary hyperparathyroidism, and the effect of 25-hydroxyvitamin D status on disease severity.
We studied 124 patients with mild primary hyperparathyroidism. Biochemical, bone mineral density, and bone histomorphometric indices were compared among patients whose serurm 25-hydroxyvitamin D levels were in the lowest and highest tertiles.
Serum 25-hydroxyvitamin D levels (mean +/- SD) were in the low range of normal (21 +/- 11 ng/mL, normal 9 to 52 ng/mL). Levels were below normal in 9 (7%) patients, and below the level suggested for vitamin D "sufficiency" (20 ng/mL) in 66 (53%) patients. Those with lowest 25-hydroxyvitamin D levels had the highest parathyroid hormone levels (low tertile 158 + 66 pg/mL versus high tertile 103 +/- 2 pg/mL, P <0.0001). Other evidence of more active hyperparathyroidism in those with low 25-hydroxyvitamin D levels included higher serum alkaline phosphatase activity (114 +/- 48 U/L versus 91 +/-35 U/L, P <0.03), lower serum phosphorus levels (2.7 +/- 0.4 mg/dL, versus 3.0 +/- 0.4 mg/dL, P <0.01), and greater bone mineral density at the lumbar spine (0.94 +/- 0.03 g/cm2 versus 0.83 +/- 0.03 g/cm2, P <0.05) reflecting the protective effects of parathyroid hormone on cancellous bone. They also had enhanced bone turnover on bone biopsy. Despite the expected differences in vitamin D metabolism in African-Americans, results did not differ by race.
Vitamin D insufficiency or deficiency is common among patients with mild primary hyperparathyroidism. In these patients, the effects of primary hyperparathyroidism on biochemical, densitometric, and histomorphometric indices are more pronounced.
The American Journal of Medicine 12/1999; 107(6):561-7. · 5.43 Impact Factor
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ABSTRACT: In the United States, most patients with primary hyperparathyroidism have few or no symptoms. The need for parathyroidectomy to treat all patients with this disorder has therefore been questioned. We studied the clinical course and development of complications for periods of up to 10 years in 121 patients with primary hyperparathyroidism, 101 (83 percent) of whom were asymptomatic. There were 30 men and 91 women (age range, 20 to 79 years). During the study, 61 patients (50 percent) underwent parathyroidectomy, and 60 patients were followed without surgery.
Parathyroidectomy in patients with or without symptoms led to normalization of serum calcium concentrations and a mean (+/-SE) increase in lumbar-spine bone mineral density of 8+/-2 percent after 1 year (P=0.005) and 12+/-3 percent after 10 years (P=0.03). Bone mineral density of the femoral neck increased 6+/-1 percent after 1 year (P=0.002) and 14+/-4 percent after 10 years (P=0.002). Bone mineral density of the radius did not change significantly. The 52 asymptomatic patients who did not undergo surgery had no change in serum calcium concentration, urinary calcium excretion, or bone mineral density. However, 14 of these 52 patients (27 percent) had progression of disease, defined as the development of at least one new indication for parathyroidectomy. All 20 patients with symptoms had kidney stones. None of the 12 who underwent parathyroidectomy had recurrent kidney stones, whereas 6 of the 8 patients who did not undergo surgery did have a recurrence.
In patients with primary hyperparathyroidism, parathyroidectomy results in the normalization of biochemical values and increased bone mineral density. Most asymptomatic patients who did not undergo surgery did not have progression of disease, but approximately one quarter of them did have some progression.
New England Journal of Medicine 11/1999; 341(17):1249-55. · 53.30 Impact Factor
