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Stephen J Gallacher, Robert A Cowan, William D Fraser, Fraser C Logue, Andrew Jenkins, and Iain T Boyle

Gallacher SJ, Cowan RA, Fraser WD, Logue FC, Jenkins A. Boyle IT. Acute effects of intravenous 1α-hydroxycholecalciferol on parathyroid hormone, osteocalcin and calcitriol in man. Eur J Endocrinol 1994;130:141–5. ISSN 0804–4643

The acute effects of a single intravenous injection of 2 μg of 1α-hydroxycholecalciferol (alfacalcidol) were studied for a 24-h period in six normal males (mean age 33 years), six women with primary hyperparathyroidism (mean age 72 years) and six women with established osteoporosis (mean age 63 years). In all three groups, serum calcitriol levels rose to a peak 2–3 h after administration of alfacalcidol. Basal levels were highest in the primary hyperparathyroidism group at (mean ±sem) 81±2 vs 62±12 (normal males) (p<0.05) and 56±5 pmol/l (osteoporosis) (p<0.01). Highest peak levels were found also in the primary hyperparathyroidism group at 150±15 vs 114±15 (normal males) (p<0.05) and 127 ± 1 5 pmol/l (osteoporosis) (p<0.01). The rise in calcitriol was higher in the primary hyperparathyroidism group than either the normal males or osteoporotic patients (p<0.05). No significant differences were evident in basal serum calcidiol concentrations among the three treatment groups. As might be expected, highest basal concentrations of parathyroid hormone (PTH). serum calcium and serum osteocalcin were noted in the primary hyperparathyroid group (PTH: 17.1±7.7 vs 1.9±0.5 (normal males) (p<0.01) and 2.1±0.3 pmol/l (osteoporosis) (p<0.01): calcium: 3.06±0.08 vs 2.50±0.02 (normal males) (p<0.01) and 2.43±0.02 mmol/l (osteoporosis) (p<0.01): osteocalcin: 1.10±0.08 vs 0.56±0.16 (normal males) (p<0.05) and 0.53±0.21 nmol/l (osteoporosis) (p<0.05). Following treatment with alfacalcidol, no significant change was observed in PTH, calcium or osteocalcin serum concentrations in any group. These results show that maximal conversion of alfacalcidol to calcitriol occurs within a few hours of administration of alfacalcidol in normal males and patients with primary hyperparathyroidism and osteoporosis. Whilst this may reflect differences in activity of the enzyme 2 5-hydroxylase among these groups, other explanations, such as differences in calcitriol clearance, cannot be excluded.

SJ Gallacher, University Department of Medicine, Queen Elizabeth Building, Glasgow Royal Infirmary, 10 Alexandra Parade, Glasgow G31 2ER, UK

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Stephen J Gallacher, William D Fraser, Owen J Owens, Frances J Dryburgh, Fraser C Logue, Andrew Jenkins, James Kennedy, and Iain T Boyle

Gallacher SJ, Fraser WD, Owens OJ, Dryburgh FJ, Logue FC, Jenkins A, Kennedy J, Boyle IT. Changes in calciotrophic hormones and biochemical markers of bone turnover in normal human pregnancy. Eur J Endocrinol 1994;131:369–74. ISSN 0804–4643

Plasma concentrations of parathyroid hormone-related protein (PTHrP), parathyroid hormone, alkaline phosphatase, osteocalcin and albumin-adjusted calcium were measured along with nephrogenous cyclic adenosine monophosphate (NcAMP) in 10 normal women longitudinally through pregnancy. In addition, an assessment of bone resorption was made in these same subjects by the measurement in true fasting urine specimens of the calcium/creatinine ratio (Ca/Cr), hydroxyproline/ creatinine ratio (HP/Cr), pyridinoline/creatinine ratio (Pyr/Cr) and deoxypyridinoline/creatinine ratio (Dpyr/Cr). The PTHrP level rose through pregnancy from (mean±sem) 0.8 ± 0.2 pmol/l in the first trimester to 2.7 ± 0.2 pmol/l 6 weeks postpartum (p < 0.0001). Serum alkaline phosphatase rose from 94 ± 8 U/l (first trimester) to 347 ± 25 U/l at term (p < 0.0001). A significant positive correlation was evident between PTHrP and alkaline phosphatase up to term (r = 0.44, p < 0.005). Parathyroid hormone concentrations remained unchanged during pregnancy but rose significantly postpartum from 1.8 ± 0.2 pmol/l (first trimester) to 3.1 ± 0.5 pmol/l (p < 0.0001). Similarly, osteocalcin, a marker of bone formative activity, remained unchanged through pregnancy but rose significantly at 6 weeks after delivery to 0.38 ± 0.05 nmol/l from 0.19 ± 0.03 nmol/l (first trimester) (p = 0.019). No significant change was noted in serum-adjusted calcium or NcAMP, either through pregnancy or at the postpartum assessment. Fasting urinary Ca/Cr fell through pregnancy from 0.70 ± 0.11 (first trimester) to a nadir of 0.19 ± 0.04 6 weeks postpartum (p = 0.007). Fasting urinary HP/Cr rose from 0.026 ± 0.003 (first trimester) to a peak of 0.049 ± 0.012 (third trimester), thereafter falling to 0.024 ± 0.002 6 weeks after delivery. Fasting urinary Pyr/Cr rose from 30.5 ± 1.7 (first trimester) to a peak of 58.3 ± 6.6 (term) (p = 0.009); Dpyr/Cr also increased through pregnancy from 9.9 ± 1.3 (first trimester) to 16.1 ± 1.7 (term) (p = 0.01). Previous studies have suggested that the placenta (during pregnancy) and breast milk (postpartum) are the main sources of PTHrP in pregnancy. This study illustrates that changes in plasma concentrations of PTHrP also can be demonstrated— although whether or not circulating PTHrP has a specific endocrine function is not clear.

SJ Gallacher, University Department of Medicine, Queen Elizabeth Building, Glasgow Royal Infirmary, 10 Alexandra Parade, Glasgow G31 2ER, UK

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Rong Huang, Yu Dong, Anne Monique Nuyt, Emile Levy, Shu-Qin Wei, Pierre Julien, William D Fraser, and Zhong-Cheng Luo

Objective: Large birth size programs an elevated risk of type 2 diabetes in adulthood, but data are absent concerning glucose metabolic health impact in infancy. We sought to determine whether large birth size is associated with insulin resistance and β-cell function in infancy, and evaluate the determinants.

Design and Participants: In the Canadian 3D birth cohort, we conducted a nested matched (1:2) study of 70 large-for-gestational-age (LGA, birth weight >90th percentile) and 140 optimal-for-gestational-age (OGA, 25th-75th percentiles) control infants. The primary outcomes were homeostasis model assessment of insulin resistance (HOMA-IR) and beta-cell function (HOMA-β) at age 2-years.

Results: HOMA-IR and HOMA-β were similar in LGA and OGA infants. Adjusting for maternal and infant characteristics, decelerated growth in length during early infancy (0-3 months) was associated a 25.8% decrease (95% confidence intervals 6.7-41.0%) in HOMA-β. During mid-infancy (3-12 months), accelerated growth in weight was associated with a 25.5% (0.35-56.9%) increase in HOMA-IR, in length with a 69.3% increase (31.4-118.0%) in HOMA-IR and a 24.5% (0.52-54.3%) increase in HOMA-β. Decelerated growth in length during late infancy (1-2 years) was associated with a 28.4% (9.5-43.4%) decrease in HOMA-IR and a 21.2% (3.9-35.4%) decrease in HOMA-β. Female sex was associated with higher HOMA-β, Caucasian ethnicity with lower HOMA-IR, and maternal smoking with lower HOMA-β.

Conclusions: The study is the first to demonstrate that large birth size is not associated with insulin resistance and β-cell function in infancy, but infancy growth pattern matters. Decelerated infancy growth may be detrimental to beta-cell function.