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We determined the relationship between patients' socioeconomic status and discussions with their primary care physicians about hormone replacement therapy (HRT) among women facing a decision about HRT within the prior year. The study included telephone interviews and medical record reviews. The setting was a general medicine practice of an urban teaching hospital in Boston, Mass. Women ages 50-65 visiting an academic teaching practice over a 3-month period were selected randomly. Of the 198 potential subjects, 118 (60%) agreed to participate in the survey. We examined discussions of HRT by women who had faced the decision to initiate HRT within the previous year. Women who were not on HRT or had been on therapy for less than 1 year were asked if they had discussed HRT with their physician in the past year. Socioeconomic factors and comorbidities were elicited during the survey and abstracted by chart review. The mean age of the 118 participants was 57; 36% were black, 54% were white, 10% were other race, 17% had less than a high school education, 14% had diabetes, 31% had had a hysterectomy, and 7% had a history of breast cancer. Of the 80 women who did not use HRT or had used it for less than 1 year, 49 (61%) reported a discussion of HRT. In bivariable analysis, patients of white race were more likely to report a discussion than black patients (72% versus 43%, odds ratio [OR] 3.6, 95% confidence interval [CI] 1.3-9.7). After adjustment for history of osteoporosis and age, white patients were more likely to report a discussion (adjusted OR 3.3, 95% CI 1.1-9.8). Further adjustment for the presence of 2 or more cardiac risk factors did not change the result. Neither level of education nor family income were significantly associated with HRT discussion. Compared with white women, the African-American women we studied were less likely to discuss HRT with their physicians. Further study is needed to determine whether the failure to discuss HRT is due to failure to initiate a discussion on the part of patients, physicians, or both.

Diabetes complicates 4% of all pregnancies is the United States and is a significant cause of maternal and fetal morbidity.1 The majority (88%) of diabetes cases in pregnancy are due to gestational diabetes which is associated with increased BMI and increased age. The remaining 12% are due to type 1 and type 2 diabetes, often referred to as pregestational diabetes. Patients with gestational diabetes usually develop hyperglycemia during the second half of pregnancy. Hyperglycemia at this stage of gestation clearly causes fetal macrosomia and neonatal hypoglycemia. Patients with pregestational diabetes are at risk for hyperglycemia early in pregnancy; this hyperglycemia is associated with significantly increased rates of fetal loss and fetal malformation. The evidence that has accrued over the past twenty years reveals that tight glycemic control can prevent most of the maternal and fetal complications of diabetes. The neonatal death rate in pregnancies complicated by diabetes was 50% prior to the introduction of insulin, 10% in 1939 after the introduction of insulin, and approached that in non-diabetic pregnancies by the 1980s.2

We describe the effects of the overexpression of noggin, a bone morphogenetic protein (BMP) inhibitor, on osteoblast differentiation and bone formation. Cells of the osteoblast and chondrocyte lineages, as well as bone marrow macrophages, showed intense beta-gal histo- or cytostaining in adult noggin+/- mice that had a LacZ transgene inserted at the site of noggin deletion. Despite identical BMP levels, however, osteoblasts of 20-month-old C57BL/6J and 4-month-old senescence-accelerated mice (SAM-P6 mice) had noggin expression levels that were approximately fourfold higher than those of 4-month-old C57BL/6J and SAM-R1 (control) mice, respectively. U-33 preosteoblastic cells overexpressing the noggin gene showed defective maturation and, in parallel, a decreased expression of Runx-2, bone sialoprotein, osteocalcin, and RANK-L. Noggin did not inhibit the ligandless signaling and pro-differentiation action of the constitutively activated BMP receptor type 1A, ca-ALK-3. Transgenic mice overexpressing noggin in mature osteocalcin-positive osteoblasts showed dramatic decreases in bone mineral density and bone formation rates with histological evidence of decreased trabecular bone and CFU-osteoblast colonies at 4 and 8 months. Together, the results provide compelling evidence that noggin, expressed in mature osteoblasts, inhibits osteoblast differentiation and bone formation. Thus, the overproduction of noggin during biological aging may result in impaired osteoblast formation and function and hence, net bone loss.

Publisher Summary This chapter reviews the cellular and molecular mechanisms that have recently been discovered regarding the bone loss associated with calcineurin inhibitors. Calcineurin inhibitors are widely used in the management of auto-immune disorders and have revolutionized organ transplantation. A direct causative role for calcineurin inhibitors has been difficult to demonstrate in clinical studies as a result of the concomitant use of glucocorticoids. The rapid and severe bone loss that occurs after organ transplant is likely to be attributable not only to glucocorticoids, but also to calcineurin inhibitors, CsA and FK506. These agents block T-cell proliferation by inhibiting the Ca++++-calmodulin-sensitive phosphatase calcineurin. These drugs have been shown to cause high-turnover bone loss in both human and animal studies. Animal studies have demonstrated acute increases in bone remodeling, consisting of both osteoclast activation and, in some circumstances, increases in osteoblastic bone formation. There is limited but persuasive evidence that T cells may mediate the action of both CsA and FK506, but again, this needs further confirmation.

Amgen Inc and Kirin Brewery Co Ltd, under license from NPS Pharmaceuticals Inc, are developing cinacalcet hydrochloride, the lead compound in a series of calcimimetics, for the potential treatment of primary and secondary hyperparathyroidism. Tecalcet hydrochloride was the first compound from this class to be extensively studied and most of the pharmacological data disclosed is for this compound. Cinacalcet hydrochloride was developed in an effort to improve on the poor pharmacokinetics and metabolism of tecalcet hydrochloride.