J. Jones

Antenatal corticosteroid therapy and risk of osteoporosis.

Objective To assess the risk of maternal osteoporosis associated with antenatal corticosterioid administration for neonatal respiratory distress syndrome prophylaxis.

A longitudinal study of biochemical markers of bone turnover during normal pregnancy and pregnancies complicated by pre-eclampsia

Objectives To test the hypothesis that the increased bone turnover observed in established pre‐eclampsia is present earlier in pregnancy prior to the diagnosis of pre‐eclampsia.

Biochemical markers of maternal bone turnover are elevated in pre‐eclampsia

Objectives To investigate the hypothesis that bone turnover is reduced in pre‐eclampsia compared with normal pregnancy.

Insulin resistance and pre-eclampsia: a role for tumor necrosis factor-α?

Insulin resistance occurs in pre-eclampsia, but the cause is unknown. Furthermore, it is uncertain whether women destined to develop pre-eclampsia have a pre-existing insulin resistance or whether it is acquired with the development of the disease. We carried out this study to test the hypotheses that the increase in insulin resistance associated with pre-eclampsia is related to higher levels of tumor necrosis factor (TNF)-α, and that the increase in insulin resistance precedes the clinical onset of the disease. Fasting plasma samples were obtained from ten women who subsequently developed pre-eclampsia and ten normal pregnant controls at 16, 20, 24, 28, 32 and 36 weeks gestation to measure circulating levels of insulin, glucose and TNF-α. Fasting insulin resistance index (FIRI) was calculated from insulin and glucose concentrations. In the normal controls, fasting insulin and TNF-α levels, and FIRI increased with gestation, and these were significantly greater than baseline values from 24, 28 and 28 weeks, respectively. In the group of women who developed pre-eclampsia, plasma levels of insulin and the FIRI were significantly higher than baseline from 20 and 24 weeks, respectively, but both were significantly higher than in the control group at 32 and 36 weeks. The increase in TNF-α in the pre-eclampsia group was significantly greater than in normal pregnant controls (p<0.001). However, there was no significant association between TNF-α levels and FIRI in either normal pregnancy or pregnancies developing pre-eclampsia. These data suggest that insulin resistance in pre-eclampsia precedes the clinical onset of the disease, but that it is not related to elevated levels of TNF-α.

Comparison of the biochemical effects of testosterone and estrogen on bone markers in surgically menopausal women

Twenty-five women with a previous total abdominal hysterectomy with bilateral salpingo–oophorectomy (TAH BSO) were given estradiol 50 mg implants at baseline, followed at 16 weeks with the combination of estradiol 50 mg and testosterone 100 mg. Blood samples were taken at 8-weekly intervals over 32 weeks. Serum levels of estradiol, testosterone, sex hormone binding globulin (SHBG) and agents involved in skeletal growth (growth hormone (GH), insulin-like growth factor 1 (IGF-1), carboxy terminal pro-peptide of type 1 pro-collagen (PICP; a bone formation marker) and cross-linked carboxy terminal telopeptide (ICTP; a marker of bone resorption)) were measured. Serum PICP levels increased significantly after estradiol alone (p = 0.0032) but the addition of testosterone had no significant effects on bone markers GH and IGF-1. These biochemical changes confirm previous studies, which found that the addition of testosterone did not augment the effect of estradiol implants on bone mineral density. Although physiological hormone replacement therapy in oophorectomized women would include replacement of both estradiol and testosterone, this may not to be necessary for prevention of osteoporosis where adequate serum estradiol levels are reached.

Maternal and fetal plasma levels of markers of bone metabolism in gestational diabetic pregnancies

The aim of this study is to determine whether gestational diabetes has any effect on maternal and fetal bone metabolism. We collected maternal and umbilical cord blood samples from 19 women with gestational diabetes and 19 controls at the time of delivery. The plasma levels of carboxy terminal pro-peptide of type I pro-collagen (PICP) and cross-linked carboxyterminal telopeptide of type I collagen (ICTP) were used to monitor the rate of bone formation and degradation respectively. There is a significant correlation between the 1 hour postprandial blood glucose and the maternal levels of ICTP (r = 0.560, P = 0.004), but there was no significant difference in maternal or fetal levels of PICP and ICTP between the study and control groups (P = 0.411 maternal PICP, P = 0.241 maternal ICTP, P = 0.365 fetal PICP and P = 0.781 fetal ICTP). In the gestational diabetes group, there was a significant correlation between maternal and fetal ICTP (r = 0.694, P = 0.001), but there was no correlation between maternal and fetal levels of PICP (r = 0.334, P = 0.175). Although the maternal levels of ICTP is related to the 1 hour postprandial blood glucose level, gestational diabetes does not affect the maternal or umbilical cord levels of the serum markers of bone metabolism.

Fetal bone metabolism in normal and rhesus isoimmunised pregnancies

Objective To construct gestation‐specific reference intervals for fetal concentrations of biochemical markers of bone metabolism and assess the effect of rhesus isoimmunisation on these.

Low dose 25 mg oestradiol implants and 1 mg norethisterone as continuous combined hormone therapy: a prospective study

The anxiety regarding no‐bleed regimens is that breakthrough bleeding and endometrial hyperplasia may occur. We aimed to demonstrate that 25 mg oestradiol implants can be adequately opposed by a low dose of progestogen protecting against osteoporosis. Twenty‐two patients were recruited to the study. The mean age was 62 years and body mass index of 26.5. Median oestradiol rose from 77 pmol/L at baseline to 275 pmol/L at one year. Median endometrial thickness remained unchanged at 4 mm and only two women withdrew with bleeding problems. There was one case of proliferative endometrium at one year—all others samples were either atrophic or secretory. Lumbar bone density (L2–L4) rose significantly from 0.939 to 0.992 g/cm2 (+5.6%, P= 0.005) and the total femoral density rose from 0.872 to 0.890 g/cm2 (+2.1%). Bone formation markers increased significantly (serum type 1 procollagen C terminal peptide, P1CP = 112–114, P= 0.0376) and bone resorption fell (serum type 1 collagen C terminal telopeptide, 1CTP = 3.0–2.9, P= 0.2863). E25 implants and low dose progestogen appear to avoid endometrial hyperplasia and bleeding problems while increasing bone density.

Increased Maternal Bone Formation in Type I Diabetic Pregnancies

Abstract. There is evidence that infants of insulin-dependent diabetics have increased intrauterine bone resorption and reduced bone mineral content at birth. The aim of this study was to determine if type I diabetes is associated with abnormal maternal bone metabolism. We measured the circulating levels of carboxyterminal propeptide of type I procollagen (PICP) and cross-linked carboxyterminal telopeptide of type I collagen (ICTP) in the third trimester of pregnancy in samples obtained from 19 pregnant women with type I diabetes and 19 pregnant controls, to monitor the rate of bone formation and degradation, respectively. Diabetic control was considered to be good as the mean hemoglobin A1 level was less than 8.5%. The circulating levels of PICP were significantly higher in pregnant women with insulin-dependent diabetes than in controls with uncomplicated pregnancy (median IDDM 147 μg/liter, control 115 μg/liter, P= 0.0014), but there was no significant difference in the circulating levels of ICTP between the two groups (median IDDM 4.6 μg/liter, control 4.6 μg/liter, P= 0.907). Therefore, our findings suggest that there is an increase in bone formation in pregnant women with type I diabetes which may be related to the increased amount of insulin administered and the improvement in diabetic control associated with pregnancy.

A highly sensitive cytochemical bioassay for plasma angiotensin II.

A highly sensitive cytochemical bioassay has been developed for measuring angiotensin II in human plasma. The assay depends on the ability of angiotensin II to alter the reducing potency of the zona glomerulosa as measured by Prussian blue staining and microdensitometry. An inverse correlation between the intensity of the stain and the logarithm of concentration existed over the range 0.05‐5.0 fmol/l of angiotensin II. The limit of sensitivity of the assay in plasma was 50 fmol/l; the index of precision was 0.07 ± 0.04 (mean ± SD; n = 15); and the coefficient of variation of a quality control sample was 34%. The response was specific for angiotensin II; approximately 102 times more angiotensin III and approximately 106 times more ACTH was required to produce a similar effect. Angiotensin I had no significant activity. A significant inverse relationship existed between sodium intake and bioactive angiotensin II in 5 normal subjects studied on low, normal and high sodium diets. Extremely low levels of angiotensin II were detected in anephric subjects.