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

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  –2.5 or T-score ≤ –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, Fa, shear force, Fs, moment, M, local curvature, θrel, 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, θrel, 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