Endocrine Abstracts

Osteoblasts and adipocytes are derived from the same stem cell in adult marrow and plasticity exists between the two lineages. In Osteoporosis there are reduced osteoblast numbers and increased adipocyte numbers suggesting a disturbance in the normal balance of the cells' differentiation pathways, leading to defective osteoblastogenesis and favouring adipogenesis. The stage of adipocytic differentiation at which plasticity is lost and commitment is established is not known. We...

BACKGROUND: Acromegaly is associated with abnormal bone metabolism, characterized by increased bone turnover. In health, PTH is secreted in a circadian rhythm, which is important in bone function. However, the effect of acromegaly on PTH secretion is unclear, with previous studies reporting increased, decreased or no change in PTH concentration. Furthermore, the presence of PTH circadian rhythmicity has not been defined in acromegaly.OBJECTIVES: To determine the effect of ...

The calcium sensing receptor (CaSR) plays a central role in altering the secretion of parathyroid hormone (PTH) in response to alterations in extracellular calcium, and four studies have reported an association between CaSR polymorphisms and serum Ca 2+, serum PTH, and bone mineral density (BMD). However, two other studies have failed to detect such associations. We have therefore undertaken studies to investigate the Ala986Ser, Arg990Gly, and Gln1011Glu CaSR polymo...

IntroductionWe have previously demonstrated profound effects of hormone replacement treatment (HRT) in post-menopausal women on the IGF-system. HRT is widely used to prevent osteoporosis. The IGF-system has been implicated in bone formation. IGFBP-4 and IGFBP-5 are known to be important in modulation of IGF activity in bone. In this larger study we have examined the effects of HRT on circulating IGFBP-4 levels.MethodOral conjugated equine estrogen (CEE) alone or in...

The discovery of the fundamental involvement of receptor activator for nuclear factor-KB ligand (RANKL) in osteoclast (OC) formation, has enabled the routine generation of human OCs in vitro from human peripheral blood mononuclear cells (PBMCs). Beta C-terminal telopeptide (beta-CTx) is a specific resorption marker for degradation of bone type I collagen by OCs. We have evaluated the correlation between beta-CTx released from dentine wafers on which OC were c...

BACKGROUND: AGHD is associated with increased prevalence of osteoporosis. Alterations in both parathyroid gland sensitivity to changes in calcium concentration and end-organ response to the effects of PTH play a role in the development of osteoporosis.OBJECTIVES: To investigate the effects of PTH (1-34) infusion on end-organ and parathyroid gland responsiveness.METHODS: 6 patients with severe AGHD were recruited. All patients were admitted, prior to commencement of GH ...

T3 and fibroblast growth factors (FGFs) are critical regulators of chondrocyte proliferation during bone formation and we identified recently that T3 modulates skeletal FGF receptor-1 (FGFR1) activity. FGFRs signal via several routes including mitogen-activated protein kinase (MAPK), STAT and phospholipase C gamma pathways. Mechanisms determining which pathways are activated by FGFRs are poorly understood but include alternative splicing of exons encoding variable domains with...

Background: Dexamethasone (Dex) induced growth retardation in children is partly mediated by direct growth plate effects. In contrast, IGF-I induces bone growth and may ameliorate these effects.Aims: To determine the direct effects of Dex and IGF-I on bone length, cell proliferation and mineralisation in cultured fetal mouse metatarsals.Methods: 18-day-old fetal metatarsals were cultured in triplicate in serum-free medium for 12 days supplemented with either Dex 10<sup...

BACKGROUND: AGHD is associated with reduced BMD. GHR results in improvement in BMD, however, some patients remain osteopaenic despite all appropriate pituitary hormone replacement. PTH plays an important role in bone metabolism, with anabolic effects following intermittent administration. To date the difference in PTH activity and phosphocalcium metabolism between fully replaced AGHD patients with normal and reduced BMD has not been investigated.OBJECTIVES: To determine th...

SHOX has been implicated in the regulation of bone growth and modelling. Haploinsufficiency and heterozygous mutations of SHOX are associated with Lerri Weil Dyschondrosteosis (LWD). The cardinal features of LWD are mesomelic limb shortening and Madelung deformity. Histological studies demonstrate premature fusion of the ulna border of the radial epiphysis and disordered osteoblast maturation and orientation. In view of these observations we investigated the role of SHOX in th...

BACKGROUND: AGHD is associated with osteoporosis. Alterations in parathyroid gland responsiveness to changes in calcium concentration play a role in the genesis of osteoporosis.OBJECTIVES: To investigate PTH response to hypo- and hypercalcaemic stimuli in AGHD.METHODS: 12 patients with untreated AGHD were consented to the study. Venous cannulae were inserted in each arm and half-hourly blood samples collected between 0900-1800hours for PTH, calcium and albumin. After 5...

The relationship between vitamin D deficiency and markers of bone metabolism is well established. We assessed, as part of the first Iranian National Osteoporosis Plan (INOP-1), the association between vitamin D deficiency and markers of bone metabolism. 1200 adult men and women, aged 20-69 years, were selected at random for this study in March 2001. Each participant provided a fasting blood sample for measurement of 25(OH)D, PTH, Ca, P, alkaline phosphatase, albumin and total ...

Introduction: Hypophosphatemic rickets is uncommon and is either genetic, usually of the X-linked kind (OMIM 307800)or acquired, often related to underlying malignancy (tumor-induced osteomalacia, TIO). Adult-onset cases of unknown aetiology have been described, although they are uncommon.I report such a case occuring after pregnancy.Case Report: A 39 year-old Serbian woman developed proximal limb weakness and limb girdle pain 6 months after a normal vaginal delivery of a ...