Bone mineral density in patients with nonalcoholic steatohepatitis among end-stage liver disease patients awaiting liver transplantation.

OBJECTIVE: Several studies have shown that patients with end-stage liver disease (ESLD) have lower bone mineral density (BMD) and a higher prevalence of osteoporosis compared to an age-matched population. Hyperinsulinemia and insulin resistance are typically associated with increased BMD. We hypothesized that patients with nonalcoholic steatohepatitis (NASH) and underlying insulin resistance may have higher BMD than patients with cirrhosis from other causes. METHODS: We performed a retrospective chart review of patients with ESLD who underwent liver transplant evaluation at Ochsner Clinic Foundation and had a BMD study as part of initial work up and compared BMD values of patients diagnosed with NASH to patients with cirrhosis due to other causes. Patients were categorized into 3 groups based on the etiology of their liver disease as NASH, alcoholic cirrhosis, or viral hepatitis C or B (HCV/HBV). RESULTS: A total of 63 patients met the study inclusion criteria, including 15 with NASH, 17 with alcoholic cirrhosis, and 31 with HCV/HBV. The overall prevalence rates of osteopenia and osteoporosis were 44% and 12%, respectively. BMD values were higher in the NASH group than the HCV/HBV group at lumbar spine, total hip, and femoral neck (P = .01, .03, and .02, respectively). There were no statistical differences in BMD values between NASH and alcoholic cirrhosis groups at any site. CONCLUSIONS: We found a high prevalence of low BMD among patients with ESLD awaiting liver transplantation. NASH patients had higher BMDs than HCV/HBV patients. The effects of NASH and insulin resistance on bone are complex and should be examined further.

Bone formation markers in patients with glucocorticoid-induced osteoporosis treated with teriparatide or alendronate.

Reduced osteoblast function is a primary defect in glucocorticoid-induced osteoporosis (GIO), and is reflected by decreased biochemical markers of bone formation, such as serum osteocalcin (OC) and procollagen type I N-terminal propeptide (PINP). This analysis compared the effects of teriparatide and alendronate on OC and PINP in patients with GIO. In a double-blind study, women (N=159) and men (N=38) with GIO were randomized to either teriparatide 20 mug/day by subcutaneous injection or to alendronate 10 mg/day orally. OC and PINP were measured in fasting-state serum samples obtained at baseline and at 1, 6, 18, and 36 months. Baseline bone formation markers were below the reference interval (low) in 33% of patients for OC and in 4% of patients for PINP. On teriparatide therapy, the median OC and PINP levels increased by 92% and 108%, respectively, and this resulted in only 12% and 1% of patients being low at 6 months. On alendronate therapy, the median OC and PINP levels decreased by 40% and 53%, respectively, and this resulted in 68% and 34% of patients being low at 6 months. We conclude that bone formation as determined by surrogate markers was increased in teriparatide-treated patients with GIO and decreased in alendronate-treated patients with GIO.

Correlations between biochemical markers of bone turnover and bone density responses in patients with glucocorticoid-induced osteoporosis treated with teriparatide or alendronate.

The purpose of this post hoc analysis was to determine whether baseline concentrations or early changes in serum bone turnover markers were correlated with changes in bone mineral density (BMD) at 18 months in patients with glucocorticoid-induced osteoporosis (GIO) treated with teriparatide (n=80; 20 mug/day) or alendronate (n=77; 10 mg/day). Bone markers included type I collagen N-terminal propeptide (PINP), type I collagen C-terminal propeptide (PICP), bone alkaline phosphatase (bone ALP), and cross-linked C-telopeptide of type I collagen (Sbeta-CTX). The relationship between baseline and early changes in markers and the 18-month changes in lumbar spine (LS) and femoral neck (FN) BMD was evaluated using Spearman correlation analysis. In the teriparatide group, increases in LS and FN BMD at 18 months were not significantly correlated with baseline marker concentrations (P>0.05) but were correlated with the increases in PINP at 1 and 6 months (P<0.05). In the alendronate group, the increase in FN BMD at 18 months was positively correlated with baseline marker concentrations (P<0.05) and negatively correlated with change in PINP and Sbeta-CTX at 1 and 6 months. In addition, in the alendronate group, the increase in LS BMD was negatively correlated with change in Sbeta-CTX at 1 month (P<0.05). Increases in BMD at the spine and hip were independent of baseline bone turnover in the teriparatide group, while increases in hip BMD were dependent on baseline bone turnover in the alendronate group. With both therapies, early changes in some bone turnover markers were correlated with 18-month gains in BMD in patients with GIO.

The effects of anti-resorptive therapies and estrogen withdrawal in adult scoliosis measured by sub-segmental vertebral BMD analysis.

The sub-segmental analysis of dual energy X-ray absorptiometry (DXA) scans from scoliotic vertebrae has established that there are differences in bone mass between the concave and convex sides of the vertebrae. Furthermore, these differences persisted in patients with low bone mass and were related to the geometry and applied loads, suggesting that this is a good model of bone adaptation in response to external stimuli. The goal of this study was to characterize the response of the human scoliotic spine to anti-resorptive treatments and estrogen withdrawal on the concave and convex sides of the spine. A total of 576 vertebrae (199 no treatment, 214 bisphosphonate, 69 estrogen and 94 estrogen withdrawal) were analyzed from 167 postmenopausal, Caucasian women. An analysis of variance (ANOVA) was used in conjunction with post-hoc Tukey tests to examine the effects of concavity, treatment group, and age. We found that the average change in BMD per year was greater than zero on the concave and convex sides with the exception of the estrogen withdrawal group. Discontinuing estrogen therapy caused patients to maintain bone mass on the concave side, but lose substantial bone density on the convex side. A differential response was also observed with respect to age. Patients younger than 60 exhibited a decrease in total BMD per year concomitant with a small degree of straightening, while those who were 60 or over demonstrated an increase in bone mass and a slight increase in the deformity. Based on these data, it is clear that the differences in BMD between the concave and convex sides of the vertebrae are not simply a result of the deformity, but more likely due to bone accretion. Further study is needed to elucidate the relationship between biomechanical forces and the adaptive response in the spine as a function of time.

Relationship between bone mass, invasive breast cancer incidence and raloxifene therapy in postmenopausal women with low bone mass or osteoporosis.

OBJECTIVE: To evaluate the relationship between bone mass and risk of breast cancer and to determine the effect of raloxifene therapy on breast cancer incidence in women categorized by bone mass into low bone mass and osteoporosis subgroups. DESIGN: In this post hoc analysis, data were analyzed from the Multiple Outcomes of Raloxifene Evaluation (MORE) trial, enrolling postmenopausal women with low bone mass (N = 7705), and the Continuing Outcomes Relevant to Evista (CORE) trial, a follow-up to MORE enrolling 4011 MORE participants. Total follow-up was for up to 8 years. Women with a total hip bone mineral density (BMD) T-score < -1 to > -2.5 or T-score < or = -2.5 (referent, NHANES III database) were classified as having low bone mass or osteoporosis, respectively. Women with a pre-existing vertebral fracture were considered as having osteoporosis irrespective of BMD T-score. Analyses were performed for invasive breast cancers and invasive estrogen-receptor (ER) positive breast cancers. RESULTS: Women with low bone mass (N = 3829) had a twofold higher incidence of invasive ER-positive breast cancer than those with osteoporosis (N = 3836) (HR 2.13, 95% CI 1.12-4.03). The incidence of all invasive breast cancers did not differ significantly between the bone mass groups. The incidences of invasive and invasive ER-positive breast cancers were 65-78% lower in women assigned raloxifene versus placebo in both the low bone mass and osteoporosis groups (p < 0.05). CONCLUSIONS: In this post hoc analysis of postmenopausal women participating in MORE and CORE, bone mass was a predictor of invasive ER-positive breast cancer. Raloxifene treatment reduced the risk of invasive and invasive ER-positive breast cancers in women with low bone mass and those with osteoporosis. Since participants were older postmenopausal women with low bone mass, whether these findings can be generalized to other postmenopausal women is unclear.

The relationship between bone mineral density and biomechanics in patients with osteoporosis and scoliosis.

Nearly one-third of all women and one-sixth of all men over age 65 have osteoporosis, and this condition is often accompanied by lumbar scoliosis. Previous work has shown that, in a group of postmenopausal women with scoliosis and osteoporosis, both the bone mineral content (BMC) and bone mineral density (BMD) were greater on the concave side than the convex side. The goal of this study was to examine the structure-function relationships in the spines of patients with low bone mass and scoliosis using a patient-specific biomechanical model. We compared the percent change in BMC and the percent change in BMD with axial force, F(a), shear force, F(s), moment, M, local curvature, theta(rel), and the patient's age, A. We found that the percent change in BMC depended on the applied moment and the local curvature. The same dependence was observed for the percent change in BMD, but in this case, the shear force was also significantly inversely correlated. A population with femoral neck BMD with a T-score greater than -2.0 was similarly evaluated and yielded similar results. The percent change in BMD was related to M, theta(rel), A and negatively to the shear force. These results indicate that the osteoporotic spine is still able to respond to changes in the mechanical environment and provides a useful comparison between patients with osteoporosis and those with normal bone mass. In addition, this model may be a useful tool for the in vivo assessment of bone density changes in response to mechanical stimuli and drug treatments.

Assessment of bone quantity and distribution in adult lumbar scoliosis: new dual-energy x-ray absorptiometry methodology and analysis.

STUDY DESIGN: In this study, we elucidated the bone quantity and distribution in lumbar spines of a group of 176 postmenopausal women (average age 72 years) with scoliosis. SUMMARY OF BACKGROUND DATA: Adolescent idiopathic scoliosis is associated with a low bone mineral density, but the bone mineral density in adult lumbar scoliosis has not been well-characterized. METHODS: Dual-energy x-ray absorptiometry analysis of the femoral neck and lumbar spines of 176 postmenopausal women were used to assess the bone mineral density and bone mineral content at both anatomic sites. Subsegmental analysis was used to determine the bone distribution within the lumbar vertebrae. RESULTS: The lumbar spine bone mass was greater than the femoral neck as evidenced by the average lumbar spine and femoral neck T-scores, -0.493 and -1.81, and Z-scores, 1.70 and 0.12, respectively. There was also a significant correlation between the lumbar spine bone mineral density and femoral neck bone mineral density (r2 = 0.24, P < 0.0001). Individual analysis of 655 vertebrae after bisection and trisection showed that the bone mineral density of the concave side was 15% to 20% higher than the convex, and the difference between the 2 sides was at least as great for patients with low femoral neck bone mineral density as those with high femoral neck bone mineral density. CONCLUSIONS: The quantity and distribution of bone in adult scoliosis is markedly different from adolescent scoliosis. The lumbar spine bone mass is much greater than the femoral neck, and the concave side bone mass is greater than the convex. Finally, subsegmental vertebral dual-energy x-ray absorptiometry analysis may have wider applications in research and clinical settings.

A case of dopamine agonists inhibiting pancreatic polypeptide secretion from an islet cell tumor.

A patient with a large prolactinoma developed a metastatic islet cell tumor secreting pancreatic polypeptide. Dopamine agonist drugs reduced the prolactin levels to normal, caused a 7-fold decrease in the pancreatic polypeptide levels, and inhibited the liver metastases. Elevated chromogranin A levels also normalized on the higher doses of bromocriptine. Dopamine receptors are found in many endocrine tissues, and the expression of dopamine-2 receptor on endocrine tumors establishes the potential for response to dopamine agonist treatment. The relatively benign risk profile of dopaminergic agents makes further testing of these drugs to treat neuroendocrine tumors a worthwhile endeavor.