Bone mass in elderly patients with Parkinson's disease.

OBJECTIVE: The objective of the present study was to find risk factors for low bone mineral density (BMD) in patients with Parkinson's disease (PD). MATERIAL AND METHODS: Twenty-six PD patients and 26 age-and sex-matched healthy controls were assessed twice within a 1-year period. PD symptoms, body weight, body fat mass, BMD, physical activity, smoking and serum concentrations of several laboratory analyses were investigated. RESULTS: BMD in different locations was lower in PD patients compared with their controls and decreased during the investigated year. BMD was lower in PD patients with low body weight. BMD Z-score of trochanter in the PD group was directly correlated to the degree of physical activity and indirectly to the length of recumbent rest. Total body BMD Z-score in the PD group was directly correlated to the degree of rigidity. Serum 25-hydroxy-vitamin D was slightly lower in PD patients. CONCLUSION: Low body weight and low physical activity were risk factors for low BMD in PD, while rigidity seemed to be protective.

Does L-dopa treatment contribute to reduction in body weight in elderly patients with Parkinson's disease?

OBJECTIVE: Many patients with Parkinson's disease (PD) lose weight also early during the disease. The objective of the study was to investigate possible causative factors for this loss. MATERIALS AND METHODS: In this report, 28 PD patients and 28 age- and sex-matched controls were repeatedly assessed with the focus on body weight, body fat mass, dysphagia, olfaction, physical activity, PD symptomatology and drug treatment. RESULTS: Weight loss was seen in PD patients both before and during L-dopa treatment. CONCLUSION: The underlying disease could play a role, but our results also suggest that L-dopa per se could contribute to the weight loss.

Factors of importance for weight loss in elderly patients with Parkinson's disease.

OBJECTIVE: Weight loss is reported frequently in patients with Parkinson's disease (PD). The objective of this study was to find the underlying factors of this phenomenon. PARTICIPANTS AND METHODS: Twenty-six L-dopa-treated patients with PD and 26 age- and sex-matched healthy controls were assessed twice within a 1-year interval. Body weight, body fat mass, resting energy expenditure, physical activity, energy intake, thyroid hormones and cognitive function were investigated. RESULTS: Nineteen (73%) of the PD patients lost body weight, although energy intake and the time for rest increased. Weight loss was most marked in patients with more severe PD symptoms and in whom cognitive function had decreased. Multiple regression analyses showed that determinants for weight loss were female gender, age and low physical activity. CONCLUSION: Weight loss was common in PD patients, in spite of the increased energy intake and was most obvious in patients with increased PD symptoms and decreased cognitive function.

Health-related quality of life after osteoporotic fractures.

OBJECTIVE: To estimate the impact of osteoporosis fractures on health-related quality of life (HRQOL) in postmenopausal women. METHODS: To compare the impact on HRQOL of different osteoporotic fractures, 600 consecutive women 55-75 years old with a new fracture (inclusion fracture) were invited by mail. After exclusions by preset criteria (high-energy fractures, ongoing osteoporosis treatment, or unwillingness to participate), 303 women were included, 171 (56%) of whom had a forearm, 37 (12%) proximal humerus, 40 (13%) hip, and 55 (18%) vertebral fracture, respectively, and all were investigated and treated according to the current local consensus program for osteoporosis. In addition, HRQOL was evaluated by the SF-36 questionnaire and compared with local, age-matched reference material. Examinations were performed 82 days (median) after the fracture and 2 years later. RESULTS: HRQOL was significantly reduced at baseline regarding all SF-36 domains after vertebral fractures and most after hip fractures, but only regarding some domains after forearm and humerus fracture. After 2 years, improvements had occurred after all types of fractures, and after forearm or humerus fracture, HRQOL was completely normalized in all domains. However, 2 years after hip fracture, HRQOL was still below normal regarding physical function, role-physical and social function, while after vertebral fracture, scores were still significantly lower for all domains, physical as well as mental. Patients with one or more previous fractures before the inclusion fracture had lower HRQOL at baseline and after 2 years, compared with those with no previous fracture. Patients with osteoporosis (T-score <-2.5 in hip or spine) had lower HRQOL than those with normal BMD. CONCLUSION: Vertebral and hip fractures have a considerably greater and more prolonged impact on HRQOL than forearm and humerus fractures. The number of fractures was inversely correlated to HRQOL. These differences should be taken into account when making priorities in health care programs.

A dose titration model for recombinant GH substitution aiming at normal plasma concentrations of IGF-I in hypopituitary adults.

OBJECTIVE: To evaluate a dose titration model for recombinant human GH substitution in adult patients with GH deficiency, aiming at normal plasma levels of IGF-I. DESIGN AND METHODS: Eighteen patients participated and a start dose of 0.17 mg GH/day was used except by two men who started with 0.33 mg/day. To demonstrate a clear GH effect the patients were first titrated, with steps of 0.17 mg GH/day every 6-8 weeks, to IGF-I levels in the upper range of age-adjusted reference values. The GH dose was then reduced 1 dose step and kept for a further 6 months. For comparison we investigated 17 healthy control subjects. RESULTS: Plasma IGF-I was increased after 2 weeks on the start dose and did not increase further for up to 8 weeks. Women had significantly lower GH sensitivity than men measured as net increment of IGF-I on the start dose of GH. GH sensitivity was not changed by age. The plasma IGF-I levels increased from 76.3+/-47.0 (s.d.) to 237+/-97 microg/l at the end of the study (P<0.001), and similar IGF-I levels were obtained in both sexes. The maintenance median GH dose was 0.33 mg/day in males and 0.83 mg/day in females (P=0.017). The GH dose correlated negatively with age in both sexes. Body weight, very low density triglycerides, lipoprotein(a) (Lp(a)), and fasting insulin increased, whereas insulin sensitivity index (QUICKI) decreased significantly. In comparison with the controls, the patients had lower fasting blood glucose, fasting insulin and Lp(a) levels at baseline, but these differences disappeared after GH substitution. The two groups had equal insulin sensitivity (QUICKI), but 2 h oral glucose tolerance test values of blood glucose and insulin were significantly higher in the patients at the end of the study. CONCLUSIONS: In conclusion our data suggest that the starting dose of GH substitution and the dose titration steps should be individualised according to GH sensitivity (gender) and the IGF-I level aimed for (age). The reduced insulin sensitivity induced by GH substitution could be viewed as a normalisation if compared with control subjects.

Changes in hip fracture epidemiology: redistribution between ages, genders and fracture types.

After several reports of increasing hip fracture incidence some studies have suggested a trend-break. In a previous study of hip fractures we forecast a 70% increase in the total number of fractures from 1985 up to year 2000. We therefore studied the incidence trend for the last 15 years and supply a new prognosis up to year 2010. We recorded all incident hip fractures treated in the county of Ostergötland, Sweden (approximately 400,000 inhabitants) 1982-96. A total of 11,517 hip fractures in men and women aged 50 years and above were included in the study after cross-validation between a computerized register of radiologic investigations and the hospital records. The projected number of fractures up to year 2010 was estimated by a Poisson regression model, considering both age and year of fracture in every single year 1982-96 for the respective fracture type and gender, and applied to the projected population. The annual number of hip fractures increased by 39% in men and 25% in women during the study period. Amongst men, the age-adjusted incidence of cervical fractures increased from 188 to 220/100,000 and of trochanteric fractures from 138 to 170/100,000. In women the incidence of cervical fractures decreased from 462/100,000 to 418/100,000 and of trochanteric fractures from 407/100,000 to 361/100,000. Cervical/trochanteric fracture incidence rate ratio leveled off, and also the female/male fracture rate ratio declined. A prognosis assuming that the incidence development will continue as during 1982-96, and a population in agreement with the forecast, predicts that the total age- and sex-adjusted number of hip fractures will decrease by 11% up to year 2010 compared with 1996. In women and men, however, a decrease of 19% and an increase of 7% respectively were projected. If the age- and sex-specific incidence remains at the same level as at the end of the study period, no significant change in the total numbers will occur. A trend-break was thus found in hip fracture incidence for women but not for men. Whether this is due to therapeutic and/or preventive measures in women is unknown. According to the most probable scenario a substantial increase in male trochanteric fractures (36%) is expected up to 2010, while all other hip fractures in both genders will decrease by 4-32% resulting in a total reduction of 11%.

Periodontal conditions in 70-year-old women with osteoporosis.

The aim of the present study was to examine the periodontal conditions in an age cohort of 70-year-old women and compare an osteoporosis group with a control group with normal bone mineral density. 210 women 70 years old and randomly sampled from the population register of the community of Linköping were examined. Bone mineral density (BMD) of the hip was measured by dual energy X-ray absorptiometry. 19 women were diagnosed with osteoporosis (BMD below 0.640 g/cm2 in total hip). 15 of them accepted to participate in the study. As a control group 21 women with normal bone mineral density (BMD exceeding 0.881 g/cm2) were randomly selected from the initial population. The clinical examination included registration of the number of remaining teeth, dental plaque and periodontal conditions. The radiographic examination included a dental panorama and vertical bite-wing radiographs. The subjects also answered a questionnaire about their general health, age at menopause, concurrent medication, smoking and oral hygiene habits. The results from this study showed no statistically significant differences in gingival bleeding, probing pocket depths, gingival recession and marginal bone level between the women with osteoporosis and the women with normal bone mineral density. In conclusion, the present randomly selected and controlled study of osteoporotic and non-osteoporotic women, showed no statistically significant differences in periodontal conditions or marginal bone level. As periodontitis as well as osteoporosis are associated with age, our study of a well-defined age cohort is of interest, but the results should be interpreted with caution since the compared groups are small.

Bone mineral density in diagnosis of osteoporosis: reference population, definition of peak bone mass, and measured site determine prevalence.

A population-based study was performed in order to compare different definitions of peak bone mass, and to apply the corresponding T-scores for different skeletal sites to a cohort of 70-yr-old women for studying the prevalence of osteoporosis. Bone mineral density (BMD) of the hip, lumbar spine, and forearm was measured by dual X-ray absorptiometry (Hologic 4500) in 296 women ages 16-31 yr and 210 women age 70 yr. Peak bone mass occurred in women in their early 20s at the proximal femur and at 28 and 31 yr at the spine and forearm, respectively. BMD cutoff levels were compared to machine-specific cutoff values for the different sites. When applied to our cohort of 70-yr-old women, the prevalence of osteoporosis at the total hip was 9-25%, depending on which peak bone mass the T-score of -2.5 was based. The prevalence in the spine was 28-33% and in the forearm 45-67%. Osteoporosis in at least one of the three measured sites was documented in 49-72% of the population sample. Our results show that the use of T-score to define osteoporosis results in a highly different prevalence rate in a given population depending on the reference population and the skeletal sites chosen for measurement.

Three years' follow-up of bone density in adult coeliac disease: significance of secondary hyperparathyroidism.

BACKGROUND: The mechanisms of disturbances in bone mineral density (BMD) in coeliac disease are not completely understood. The aim of this prospective study was to investigate the possible significance of secondary hyperparathyroidism (SHPT) with regard to BMD in patients with untreated coeliac disease. METHODS: One hundred and five adult patients with untreated coeliac disease were examined for BMD and serum parathyroid hormone (PTH) concentration. BMD in the hip, lumbar spine, and forearm were examined up to 3 years after the introduction of a gluten-free diet. RESULTS: SHPT was found in 27% (28 of 105) of the patients. In patients with SHPT serum levels of 25-hydroxy-vitamin D were lower and those of alkaline phosphatase higher than in patients with normal PTH, but ionized serum calcium did not differ between the two groups. BMD was more severely reduced in patients with SHPT. Although the BMD increment was more rapid in patients with than in those without SPTH, only in the latter group did mean BMD became normal after 1-3 years on a gluten-free diet (GFD). After 3 years on a GFD more than half of the patients with initial SHPT still had low BMD in both the hip and the forearm. Furthermore, in patients with SHPT the intestinal mucosa more often remained atrophic at the 1-year follow-up, despite good compliance with the diet. CONCLUSIONS: Low BMD in patients with untreated coeliac disease is often associated with SHPT. After 3 years on a GFD the BMD remains low only in patients with initial SHPT. We therefore suggest that PTH should be measured when the diagnosis of coeliac disease is made, as an indicator of more serious intestinal disorder and complicating bone disease.

Low circulating insulin-like growth factor I in coeliac disease and its relation to bone mineral density.

BACKGROUND: Patients with coeliac disease have low bone mineral density (BMD), but the underlying mechanisms are unclear. Our aim was to study circulating insulin-like growth factor I (IGF-I) and its possible relationship to BMD in adults with untreated coeliac disease and after 1 year on a gluten-free diet. METHODS: In 29 consecutive adult coeliac patients fasting IGF-I and BMD (n = 28) were examined before and 1 year after starting a gluten-free diet. Intact parathyroid hormone (PTH) was measured (n = 20) before the gluten-free diet was started. RESULTS: Untreated coeliac patients had lower IGF-I values than controls matched for age and sex, and their BMD was low. A relationship was observed between BMD and IGF-I but not independent of age and body mass index. During the 1st year on a gluten-free diet BMD increased (P < 0.001), as did the circulating IGF-I levels in 21 of the 29 patients (P = 0.078). In the subgroup of 14 patients with normal initial PTH the increase in IGF-I correlated positively with the increase in BMD (femoral trochanter, r = 0.62, P < 0.05, and lumbar spine, r = 0.70, P < 0.02). CONCLUSIONS: BMD and circulating IGF-I levels are low in adults with untreated coeliac disease. In patients with normal initial PTH level there is an association between the change in BMD and circulating IGF-I, although this parallel increase may not be causally connected.

Cadmium may be a risk factor for osteoporosis.

OBJECTIVES: The primary study aim was to examine the possible role of cadmium as a risk factor for osteoporosis by determining the bone mineral density (BMD) in workers previously exposed to cadmium. A second objective was to validate the BMD data obtained with a movable instrument. METHODS: 43 workers who were exposed to cadmium for < or = 5 years before 1978 were studied. Cadmium in blood (B-Cd) and urine (U-Cd) were used as dose estimates. The BMD was assessed in the forearm, the spine, and the hip (neck and trochanter) with a dual energy x ray absorptiometry (DXA) instrument. Age and sex matched reference populations were used to compute Z scores, commonly used to assess osteoporosis. RESULTS: The mean forearm Z score was -0.60 (95% confidence interval (95% CI) -1.08 to -0.12) in the group exposed to cadmium. The mean Z score for the spine was -0.47 (95% CI -0.92 to -0.03), for the hip neck -0.40 (95% CI -0.75 to -0.05), and for the hip trochanter -0.22 (95% CI -0.52 to -0.07). The decrease in forearm BMD was correlated with age (p = 0.002) and B-Cd (p = 0.040). No such correlations were found for the other sites. Workers with tubular proteinuria had a lower forearm BMD (p = 0.029) and a lower Z score (p = 0.072) than workers without tubular proteinuria. CONCLUSIONS: There was a suggested dose-effect relation between cadmium dose and bone mineral density. Furthermore, there was a dose-response relation between cadmium dose and osteoporosis. Cadmium may be a risk factor for the development of osteoporosis at lower doses than previously anticipated.

Bone mineral density in normal Swedish women.

We examined 429 women, aged 20-80 years, randomly selected from the population register to establish normal values for bone mineral density (BMD) in Swedish women. BMD of the spine and hip was measured by dual-energy X-ray absorptiometry (DEXA; Hologic QDR 1000) and in the forearm by single photon absorptiometry (SPA; Molsgaard ND-1100). The recalled age of menarche was negatively correlated to BMD at all ages. There was no significant change in BMD from 20-49 years at any site except a slight decline at Ward's triangle. Bone loss was rapid at all sites during the first decade after menopause. Thereafter, BMD declined slowly in the trochanter and total hip but more rapidly in the forearm, femoral neck, and Ward's triangle. BMD in the spine even increased in the eighth decade probably due to osteoarthritis. The average change in forearm BMD during the 15 perimenopausal years comprising mean age for menopause +/- 2 SD (43-57 years) was -0.4% per year in premenopausal females and -1.6% per year in postmenopausal females. The corresponding annual percental change was, for the spine, +0.2 and -1.7; neck, -0.7 and -1.7; trochanter, +0.5 and -1.5; and Ward's triangle, -0.1% and -2.2%, respectively. Our normal values for lumbar spine BMD prior to menopause did not differ from published values or the manufacturer's normal values; however, our spine BMD values for the first decade after menopause were significantly lower (approximately 10%) than in other studies. Our femoral neck BMD values for younger women were, like those of several other groups, significantly lower than the manufacturer's normal values, but our sample of young women in this study was small. The prevalence of osteoporosis, if defined as t score < -2.5 is highly dependent on the sampling of the reference population of young adult women, and also on the choice of skeletal site. Further studies on bone mineral density in healthy young adult women are needed.

Logics and logistics of community intervention against osteoporosis: an evidence basis.

Under designations like small areas action research and intervention, directed 'ground-up' health promotion and prevention in the population form an important part of the ongoing medical systems development. There is recent evidence of the success of community intervention against cardiovascular disease. In osteoporosis, however, there is still a lack of conclusive data on both the logics and logistics of such an approach. Since 1988, a county health policy program has been formulated and implemented in Ostergötland, Sweden, following the principles and guidelines of the WHO HFA 2000 declaration. Vadstena (n approximately 7,600) was chosen for a local and generalizable osteoporosis prevention project mediated by the primary care organization by means of health promotion and education in the community. In the present report we emphasize that community intervention is an important new advancement of the medical systems, where the basic research questions include operational and management aspects as equally vital and measurable requisites and results as other performance and outcome variables. We found that a community intervention trial against osteoporosis is both motivated and feasible and in this report wish to provide evidence on these crucial issues of logics and logistics.

Hyperparathyroidism and long-term lithium therapy--a cross-sectional study and the effect of lithium withdrawal.

OBJECTIVES: To assess in patients with long-term lithium treatment the incidence and prevalence of hypercalcaemia and hyperparathyroidism, and to evaluate the relationship between parathyroid function and renal function: also, to examine the effect of treatment discontinuation. DESIGN: Part 1. An epidemiological cross-sectional study covering defined catchment areas. Part 2. A lithium withdrawal study in a subgroup of the patients who were examined after a mean of 8.5 (4-16) weeks off lithium. Comparisons were made with a group of psychiatric non-lithium patients matched for sex and age. SETTING: Outpatient treatment at nine psychiatric departments in southern Sweden. SUBJECTS: Inclusion criterion was 15 years or more on lithium. Excluded from Part 2 were patients with a high risk of relapse. Out of 215 identified patients. 142 (66%) entered and completed Part 1, while 13 of the latter entered and completed Part 2. RESULTS: The point prevalence of persistent hypercalcaemia was 3.6% and of surgically verified hyperparathyroidism 2.7%. The observed incidence of hyperparathyroidism over 19 years was 6.3%. It was significantly higher than expected in females. In the withdrawal group serum calcium was significantly increased compared to controls, and did not change during 8.5 weeks without lithium. Isostenuria was significantly more common among patients with than without hyperparathyroidism. CONCLUSIONS: The point prevalence, and the 19-year incidence of hyperparathyroidism, were increased. The point prevalence of hypercalcaemia was also increased, and not reversible during 8.5 weeks off lithium. The findings support the hypothesis of a causal relationship between lithium treatment and hyperparathyroidism. Hypercalcaemia and hyperparathyroidism are sometimes aetiologically related to reduced renal function in long-term lithium patients.

Reversal of osteopenia with diet in adult coeliac disease.

To evaluate the effects of a gluten free diet on bone mineral density in untreated adult patients with coeliac disease, 63 patients (17-79 years, 35 women) were examined at diagnosis and after one year taking a gluten free diet. Bone mineral density was measured in the forearm using single photo absorptiometry and in the lumbar spine, femoral neck, and trochanter using dual energy x ray absorptiometry. The values for each patient were compared with those of 25 healthy controls, matched for sex, age, and menopausal state. Before being given a gluten free diet bone mineral density in the total group was reduced at all sites (p < 0.001). Age adjusted bone mineral density was inversely correlated with age. During the first year taking a gluten free diet bone mineral density increased at all sites (p < 0.01). This was seen in patients of all ages and in patients who were without symptoms of malabsorption (weight loss or diarrhoea) before treatment. Low bone mineral density in patients with untreated coeliac disease increases rapidly when treatment with a gluten free diet is followed. These findings emphasise the importance of early diagnosis and treatment in all patients with coeliac disease.

Mutations in the human Ca(2+)-sensing-receptor gene that cause familial hypocalciuric hypercalcemia.

We report five novel mutations in the human Ca(2+)-sensing-receptor gene that cause familial hypocalciuric hypercalcemia (FHH) or neonatal severe hyperparathyroidism. Each gene defect is a missense mutation (228Arg-->Gln, 139Thr-->Met, 144Gly-->Glu, 63Arg-->Met, and 67Arg-->Cys) that encodes a nonconservative amino acid alteration. These mutations are each predicted to be in the Ca(2+)-sensing receptor's large extracellular domain. In three families with FHH linked to the Ca(2+)-sensing-receptor gene on chromosome 3 and in unrelated individuals probands with FHH, mutations were not detected in protein-coding sequences. On the basis of these data and previous analyses, we suggest that there are a wide range of mutations that cause FHH. Mutations that perturb the structure and function of the extracellular or transmembrane domains of the receptor and those that affect noncoding sequences of the Ca(2+)-sensing-receptor gene can cause FHH.

[Vitamin D and osteoporosis]. / Vitamin D och osteoporos.

Vitamin D constitutes a complex endocrine-regulated system, and is both a prohormone for the endogenous synthesis of the active hormone, calcitriol, and a vitamin which may be administered to supply the organism's requirements. No single test or investigation is available for the demonstration of vitamin D deficiency. Both vitamin D intake and ability to synthesise vitamin D decrease with increasing age, and particularly the elderly in institutionalised care are at risk of developing vitamin D deficiency. Iceland excepted, mean daily vitamin D consumption in the Nordic countries is less then 5 micrograms; and in approximately 10-25 per cent of the population, daily intake is less than 2.5 micrograms which is insufficient to maintain an adequate serum calcidiol concentration in individuals unexposed to sunlight. The recommended daily intake of 5 micrograms, currently adopted in the Nordic countries, may be too low-an intake of 10 micrograms is probably necessary to satisfy requirements in the elderly.

Bone mineral density in coeliac disease.

Patients with coeliac disease may have osteomalacia or osteoporosis, even in the absence of abdominal symptoms. Little is known about the effects of a gluten-free diet and villous restitution on the bone mineral density in adult patients with coeliac disease. Of the 288 patients with coeliac disease in our unit, 13 (5%) had persistent villous atrophy of the small bowel despite dietary recommendations over at least the previous 4 years. For each of these 13 patients, 1 or 2 controls with coeliac disease, matched for age, gender, menopausal state, and dermatitis herpetiformis, whose intestinal mucosa had normalized at least 4 years earlier, were identified (n = 17). Bone mineral density was measured in the forearm using single-photon absorptiometry and in the femoral neck and trochanter using dual-energy X-ray absorptiometry. Bone mineral density was reduced at all sites in patients with persistent villous atrophy compared with patients responsive to diet and healthy controls. Bone mineral density in patients responsive to diet did not differ from that in healthy controls. Persistent villous atrophy is associated with low bone mineral density, underlining the importance of keeping to a proper diet.

Osteoporosis, metabolic aberrations, and increased risk for vertebral fractures after partial gastrectomy.

A case-control study compared 129 men with earlier partial gastrectomy (operation during the period 1952-1961) with 216 men from a community-based population study. All were born 1910-1915 and the mean age was 72 years. Men with a previous partial gastrectomy had vertebral fractures in 19% compared with 4% (P < 0.01) in the control population. Bone mineral density (BMD) in the right calcaneus measured with dual energy photon absorptiometry was 20% lower in men with a Billroth II operation (P < 0.001) and 8% lower with a Billroth I operation (ns). In comparison with the controls, the men subjected to partial gastrectomy had higher serum concentrations of osteocalcin and alkaline phosphatase activity, a lower serum concentration of 25-hydroxyvitamin D (25OHD) and a lower body mass index (BMI). There were no difference in serum concentrations of free calcium, intact parathyroid hormone (PTH), or free thyroxine. The smoking prevalence was significantly higher in men with partial gastrectomy than in controls. Smokers had significantly lower serum concentrations of intact PTH and 25OHD than nonsmokers and also lower BMD and BMI. The relationships between intact PTH on one hand, and ionized calcium (inverse relationship) and osteocalcin (direct relationship) on the other were preserved in smokers, however. Gastroscopy was performed in 78 men with multiple biopsies in the gastric remnant and also in the small intestine. All but two subjects had chronic gastritis. Examination of sternal bone marrow smears showed that 40% of the Billroth-operated men lacked bone marrow reticular iron.(ABSTRACT TRUNCATED AT 250 WORDS)

Parathyroid hormone-related peptide, measured by a midmolecule radioimmunoassay, in various hypercalcaemic and normocalcaemic conditions.

The diagnosis of humoral hypercalcaemia of malignancy often presents considerable clinical problems. We have studied parathyroid hormone-related peptide (PTHrP) in serum from patients with humoral hypercalcaemia of malignancy (N = 22), hypercalcaemia of malignancy with skeletal metastases (17), histologically confirmed primary hyperparathyroidism (21) and hypercalcaemic patients with various benign diseases (9). PTHrP measurements were also made in normocalcaemic patients with various malignancies (23), endocrine diseases (13), sarcoidosis (22) and chronic renal failure (17). PTHrP was measured by a novel radioimmunoassay using rabbit antibodies directed towards the midregion of the molecule. Immuno- or silica cartridge extraction of serum before radioimmunoassay enabled us to measure PTHrP in all samples, which may add further information about circulating forms of PTHrP. PTHrP was clearly elevated in patients with humoral hypercalcaemia of malignancy (5.0 +/- 4.7 pmol/l) (mean +/- SD, N = 12) and when the kidney function was impaired (4.0 +/- 0.9 pmol/l) (N = 15) (silica cartridge extraction), whether the subject was hypercalcaemic or not. Some patients with endocrine diseases, including two with primary hyperparathyroidism, had slightly elevated serum PTHrP concentrations, while they were normal in sarcoidosis. In healthy subjects the levels were 1.1 +/- 0.5 pmol/l (N = 15) after immunoextraction and 0.8 +/- 0.2 pmol/l (N = 33) after silica cartridge extraction.