The serum levels of intact parathyroid hormone and cholecalciferol metabolites have been measured in patients with hip fracture above 70 years of age admitted to hospital from home-living conditions and compared with serum levels in age- and sex-matched home-living control subjects. It was found that patients with hip fracture had significantly lower levels of calcidiol (29.7±15.9 vs 46.0±27.8 nmol/l) and calcitriol (63.6±25.0 vs 91.1±39.5 pmol/l) with no difference in serum levels of intact parathyroid hormone (47.2±2.1 vs 5.3±3.3 pmol/l). The data suggest that secondary hyperparathyroidism is not an important risk factor in our population of patients with hip fracture.
Jan A Falch, Morten Mowé, Thomas Bøhmer and Egil Haug
Helge Bell, Nils Raknerud, Jan A Falch and Egil Haug
Bell H, Raknerud N, Falch JA, Haug E. Inappropriately low levels of gonadotrophins in amenorrhoeic women with alcoholic and non-alcoholic cirrhosis. Eur J Endocrinol 1995;132:444–9. ISSN 0804–4643
We investigated a group of 111 amenorrhoeic females with associated liver disease. These comprised alcoholic cirrhotics (N = 38), non-alcoholic cirrhotics (N = 12), non-cirrhotic alcoholics (N = 21) and those suffering from other chronic liver diseases (N = 40) admitted to our medical department from 1986 to 1991. The serum levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), oestradiol, testosterone, sex hormone binding globulin (SHBG) and prolactin were measured. Serum LH was decreased below the normal range in 50% of patients with alcoholic cirrhosis and in 42% of patients with non-alcoholic cirrhosis. One third of non-cirrhotic alcoholics also had decreased LH, in contrast to only 8% of patients with other chronic liver diseases (p < 0.01). A close correlation was found between LH and FSH when all patients were pooled (r = 0.91, p < 0.001). A gonadotrophin-releasing hormone (GnRH) injection elicited a clear LH and FSH response in 11 out of 14 patients with cirrhosis, indicating that the hypothalamus rather than the pituitary is the site of disturbance in gonadotrophin secretion. Serum SHBG was within normal limits and similar in all four groups. In nine females with alcoholic cirrhosis who abstained for 3 months, serum SHBG increased significantly from 39 ± 18 to 70 ± 25 nmol/l (p < 0.001), while LH increased in five of nine females and was unchanged in four. In conclusion, half of the amenorrhoeic females with alcoholic as well as non-alcoholic cirrhosis had inappropriately low serum LH and FSH levels, indicating dysfunction of the hypothalamo–pituitary axis. The GnRH test indicated that disturbed hypothalamic function was the cause of the decreased LH and FSH secretion.
Helge Bell, Department of Medicine, Aker University Hospital, Trondhjemsveien 235, 0514 Oslo, Norway
Jens P Berg, Jan A Falch and Egil Haug
Berg JP, Falch JA, Haug E, Fracture rate, pre- and postmenopausal bone mass and early and late postmenopausal bone loss are not associated with vitamin D receptor genotype in a high-endemic area of osteoporosis. Eur J Endocrinol 1996;135:96–100. ISSN 0804–4643
To investigate a possible association between vitamin D receptor genotype and development of postmenopausal osteoporosis, a longitudinal study from 1977 to 1995 was carried out on women living in Oslo, Norway. One hundred and eighteen premenopausal women born in 1930 were included in a study of pre- and postmenopausal bone loss in 1977. In 1995, blood samples for vitamin D receptor genotyping were available in 72, 42 and 49 of the women eligible for the determination of premenopausal bone mineral content, early postmenopausal appendicular bone loss and late postmenopausal bone mineral content, bone loss and fractures, respectively. Bone mineral density was measured in the distal and proximal right forearm annually from 1977 to 1987, and in the lumbar spine, proximal femur, right forearm and total body, including ultrasound measurements of the right calcaneus, in 1993 and 1995. Non-spinal fractures were also recorded. The results were compared to the individual vitamin D receptor genotype and it was found that vitamin D receptor genotype was neither associated with non-spinal fractures, pre- and postmenopausal bone mass nor with early and late postmenopausal bone loss within the age of 65 years. In conclusion, premenopausal bone mass, postmenopausal bone loss and the subsequent risk of osteoporosis and fractures were not predicted by vitamin D receptor genotype in a high-endemic area of osteoporosis.
Jens P Berg, Hormone Laboratory, Aker University Hospital, Trondheimsveien 235, N-0514 Oslo, Norway
Kristin Holvik, Haakon E Meyer, Anne Johanne Søgaard, Randi Selmer, Egil Haug and Jan A Falch
Objective: To evaluate whether Pakistanis have increased bone turnover compared with ethnic Norwegians due to their high prevalence of vitamin D deficiency and secondary hyperparathyroidism, and whether the relation between bone turnover and bone mineral density (BMD) differs between Pakistanis and ethnic Norwegians.
Design: A cross-sectional, population-based study conducted in the city of Oslo in 2000–2001. Random samples of 132 community-dwelling Pakistani men and women of ages 40, 45, and 59–60 years, and 580 community-dwelling Norwegian men and women of ages 45 and 59–60 years are included in this substudy.
Methods: Venous serum samples were drawn for measurements of markers of the vitamin D endocrine system and the bone turnover markers osteocalcin (s-OC), bone alkaline phosphatase (s-bone ALP), and tartrate-resistant acid phosphatase (s-TRACP). BMD was measured at the forearm by single-energy X-ray absorptiometry.
Results: Pakistanis had higher s-bone ALP compared with Norwegians. Mean (95% CI) age-adjusted levels were 22.5 (21.0, 24.1) U/l in Pakistani men versus 19.3 (18.6, 20.1) U/l in Norwegian men, P < 0.0005, and 20.3 (18.4, 22.1) U/l in Pakistani women versus 16.7 (16.0, 17.4) U/l in Norwegian women, P = 0.001. There tended to be an inverse association between bone turnover and BMD in men and women of both ethnic groups, and it was strongest for s-bone ALP. Overall mean (95% CI) distal BMD decrease was −16 (−20, −11) mg/cm2 per 1 s.d. increase in s-bone ALP (P < 0.0005) when adjusting for age, sex, and ethnicity.
Conclusions: Except for somewhat higher s-bone ALP levels in Pakistanis, there were only minor ethnic differences in bone turnover, despite a strikingly different prevalence of secondary hyperparathyroidism. Bone turnover was inversely associated with forearm BMD in both ethnic groups.
Kristian Løvås, Clara G Gjesdal, Monika Christensen, Anette B Wolff, Bjørg Almås, Johan Svartberg, Kristian J Fougner, Unni Syversen, Jens Bollerslev, Jan A Falch, Penelope J Hunt, V Krishna K Chatterjee and Eystein S Husebye
Patients with primary adrenal insufficiency (Addison's disease) receive more glucococorticoids than the normal endogenous production, raising concern about adverse effects on bone.
To determine i) the effects of glucocorticoid replacement therapy on bone, and ii) the impact of glucocorticoid pharmacogenetics.
Design, setting and participants
A cross-sectional study of two large Addison's cohorts from Norway (n=187) and from UK and New Zealand (n=105).
Main outcome measures
Bone mineral density (BMD) was measured; the Z-scores represent comparison with a reference population. Blood samples from 187 Norwegian patients were analysed for bone markers and common polymorphisms in genes that have been associated with glucocorticoid sensitivity.
Femoral neck BMD Z-scores were significantly reduced in the patients (Norway: mean −0.28 (95% confidence intervals (CI) −0.42, −0.16); UK and New Zealand: −0.21 (95% CI −0.36, −0.06)). Lumbar spine Z-scores were reduced (Norway: −0.17 (−0.36, +0.01); UK and New Zealand: −0.57 (−0.78, −0.37)), and significantly lower in males compared with females (P=0.02). The common P-glycoprotein (ABCB1) polymorphism C3435T was significantly associated with total BMD (CC and CT>TT P=0.015), with a similar trend at the hip and spine.
BMD at the femoral neck and lumbar spine is reduced in Addison's disease, indicating undesirable effects of the replacement therapy. The findings lend support to the recommendations that 15–25 mg hydrocortisone daily is more appropriate than the higher conventional doses. A common polymorphism in the efflux transporter P-glycoprotein is associated with reduced bone mass and might confer susceptibility to glucocorticoid induced osteoporosis.