222 Abstracts from the Bone and Tooth Society Meeting

2. T C B Stamp, M V Jenkins, M Katakity et al Bone (1988), 9: 251.

PlO. Bone loss due to hyperprolactinaemic amenorrhoea: early effects of bromocriptine C J Gibbs, J G B Millar Department of Renal and Endocrine Medicine, St Mary’s Hospital, Portsmouth

Bone loss due to hyperprolactinaemic amenorrhoea can be halted in some patients following treatment (Klibanski A NEJM 1986; 315 542-546). However, most patients with microadenomas are treated with a course of bromocriptine only long enough to restore fertility. It is not clear whether the benefits of prolonged treatment with bromocroptine outweigh the disadvantages. We studied 6 women aged 26-42 years before and after 6 months of bromocriptine treatment. Serum prolactin fell from a median of 1872mIU/L (range 894-10,400) to 225mIUL (range 79-374) (p<O.Ol). Serum oestradiol increased from 77+12pmoliL (mean+1 SD) to 414f125pmolL (p<O.Ol). Serum alkaline phosphatase fell from 79.3f11.4IU/L to 73.2+14.8IU/L. Urinary calcium/ creatinine ratio fell from 0.28kO.12 (molar ratio) to 0.20f0.12. Forearm bone density measured by single photon absorptiometry (n=5) fell from 1.00+0.14 to 0.96f0.14 (distal radius) and from 1.35kO.17 to 1.31kO.15 (radial shaft) (p<O.O5). The fall in alkaline phosphatase and the calcium retention is consistent with a fall in bone turnover due to increasing circulating oestrogen concentrations. However, bone loss occurred in the radius in the first 6 months of treatment. A short course of bromocriptine to restore fertility did not increase bone mass in this study. The effect of prolonged bromocroptine treatment, with and without oestrogen replacement needs to be investigated.

Pll. The response of acute and chronic ethanol dosage on synthetic rates of bone proteins V R Preedy*, J R Salisburyt, and T J Peters* *Departments of Clinical Biochemistry tMorbid Anatomy, King’s College School of Medicine and Dentistry, Bessemer Road, London SE5 9PJ

The aim of this study was to determine whether synthesis of bone proteins is influenced by ethanol. Fractional rates of bone protein synthesis (%/day) were measured in viva in young rats (1OOg body weight) with a flooding dose of [3H]phenylalanine. In the acute study rats received 75mmol ethanol/kg body weight ip, or isovolumetric O.l5mol/l NaCl ip for controls, 2.5hr before the study. Free phenylalanine specific radioactivities in control (n=7) and ethanol-treated rats (n=7) were 355f7dpm/nmol and 353f17 (mean + SEM) dpm/nmol, respectively. Protein-bound phenylalanine specific radioactivities were however reduced, from 1.65fO.O3dpm/nmol (controls) to 1.14fO.O6dpm/nmol (ethanol-treated, p<O.OOl). Calculated fractional rates of bone protein synthesis were reduced by 30%, when compared with saline- treated controls (p<O.OOl). The amount of bone protein synthesised per unit RNA was also reduced by 30%, (pCO.001). In rats fed a diet containing 36% of

total calories as ethanol for up to 6 weeks, rates of mixed bone protein synthesis were not significantly different to pair-fed controls. Thus, acute alcohol treatment causes impaired bone protein synthesis but after prolonged exposure adaptation ensues.

P12. Changes in bone collagen content after chronic ethanol feeding V R Preedy, C Moniz, B Hammond, D Baldwin and T J Peters Department of Clinical Biochemistry, King’s College School of Medicine and Dentistry, Bessemer Road, London SE5 9PJ

Chronic alcohol exposure causes defects in bone structure and physical properties. Previous studies have shown this may be due to reductions in bone mineral content. We investigated the possibility that perturbations of collagen metabolism may also be a contributory mechanism. Sequential changes in tibia hydroxyproline contents were determined in rats fed liquid diets containing 36% of total calories as ethanol. Controls were pair-fed with identical diets in which ethanol was substituted by isocaloric glucose. At 3,7 and 14 days the hydroxyproline concentrations (mg/g wet weight) and contents (total hydroxyproline per tibia) were unaltered (p<O.50). However, at 28 days, hydroxyproline concentration was reduced by 20%, ie from 9.15mg+0.42mg/g wet weight to %30?0.39mg/g wet weight (p=O.O35; all results are mean f SEM of 5-6 pairs of observations). Total hydroxyproline contents fell, from 2.57+0.08mg/tibia to 2.09+0.17mg/tibia (p=O.O45). There was also a decrease in the hydroxyproline/mixed protein ratio (p=O.O3). These changes may be related to the enhanced urinary hydroxyproline excretion observed at 6 weeks, ie to 135+14 (ethanol-fed) from 88+10 (controls) pmol hydroxyproline/mmol creatinine/day (p=O.O15). This suggests that alcohol feeding causes enhanced collagen degradation, though changes in collagen synthesis may also be a contributing factor. Thus, alcohol induced reductions in the collagen composition of bone may be responsible for alteration in mechanico- physical properties.

P13. 1,25(OH)2D3 receptor expression and the inhibition of c-myc mRNA in activated human tonsillar T-lymphocytes R Karmali, M Hewison, A Brennan, D R Katz, S M Farrow and J L H O’Riordan The Middlesex Hospital, London WIN 8AA

1,25(OH)2D3 inhibits proliferation of activated T cells and decreases c-myc mRNA expression in myelomonocytic cells. To study this further we have used T cells activated through different pathways.

T cells isolated from human tonsils were stimulated in the presence or absence of 1,25(OH)2D3 with phytohaemagglutinin (PI-IA), phorbol myristate acetate (PMA), anti-CD3 monoclonal antibody or calcium ionophore (A23187). After 72 hours c-myc mRNA and receptors for 1,25(OH)2D3 were measured.

PHA induced a 40-fold rise in c-myc mRNA. This rise was inhibited by 50% in the presence of 1,25(OH),D3