Cardiovascular risk factors during estrogen-norethindrone and cholecalciferol treatment.

The effect of cholecalciferol and estrogen-norethindrone treatment on total cholesterol level, high-density lipoprotein cholesterol level, blood pressure, and body mass index was investigated in 74 postmenopausal women in a double-blind, randomized trial. Blood pressure and body mass index did not change throughout the study. We demonstrated a decrease (11%) in serum cholesterol level after 1 year of treatment with estrogen-norethindrone. When this treatment was combined with cholecalciferol, a similar decrease (13%) was observed. The hypocholesterolemic effect was correlated to body mass index in a way that indicated the most pronounced decrease in lean women. The high-density lipoprotein cholesterol/total cholesterol fraction increased by 45% after 1 year of estrogen-norethindrone treatment, while an increase of 25% after 1 year was seen when cholecalciferol was added to the treatment. The latter increase was not different from a similar increase in the placebo group. The possible dyslipidemic effect of cholecalciferol, along with the risk of hypercalcemia, emphasizes the caution necessary in cholecalciferol treatment.

A sex comparison of rates of new AIDS-defining disease and death in 2554 AIDS cases. AIDS in Europe Study Group.

OBJECTIVES: To compare the development rate of new AIDS-defining diseases between 566 women and 1988 men with AIDS who were infected with HIV via the same routes (mainly by sharing drug injecting equipment and heterosexual sex). DESIGN: Information on patient follow-up after AIDS diagnosis was obtained by retrospectively reviewing case notes. METHODS: The 2554 men and women were followed from the time of AIDS diagnosis as part of the multicentre AIDS in Europe study, which examined AIDS cases diagnosed at 52 centres in 17 European countries between 1979 and 1989. Incidence of AIDS-defining diseases and demographic variables were recorded for all patients and CD4 lymphocyte count at the time of AIDS diagnosis for approximately half the patients. RESULTS: Only toxoplasmosis and herpes simplex virus ulceration showed statistically significant differences in occurrence rate between women and men [relative risks (RR), 1.51 and 3.44; 95% confidence interval (CI), 1.51 1.09-2.08 and 3.44 1.92-6.23, respectively] which remained after adjusting for imbalances in other variables. For both diseases, the additional absolute rate in women was approximately three per 100 person-years at risk. Survival after AIDS diagnosis was also similar between the two sexes (RR, 0.96; 95% CI, 0.86-1.08). CONCLUSION: There appears to be little difference between women and men in the clinical course of AIDS.

Seasonal variations in indices of bone formation precede appropriate bone mineral changes in normal men.

In 10 normal males aged 23-50 years measurements of serum alkaline phosphatase (s-AP) and the 24-h whole body retention of 99mTc-diphosphonate (WBR), as indices of bone formation, and the fasting urinary hydroxyproline:creatinine ratio (OHPr:Cr), as an index of bone resorption, were performed monthly from January 1983 to May 1984. Bone mineral content of the distal forearm (BMC) was measured in the middle of each quarter. From January to May BMC exhibited a reproducible, significant average increase of 2.5%, returning to baseline level between May and August. During the first quarter of both 1983 and 1984 a significant increase in s-AP and WBR was seen. Subsequently, during the second quarter of 1983, these variables fell below the mean of the year. Confirming their interrelationship, the deviations of s-AP and WBR were positively correlated throughout the study period (r = 0.51, P less than 0.05). Since the urinary OHPr:Cr ratio remained constant, the reported seasonal changes in bone mass of normal, adult males appear to result from primary changes in bone formation.

Thiazide for the postponement of postmenopausal bone loss.

The effect of thiazide on bone mineral loss in normal postmenopausal women was examined during a 3 yr placebo-controlled clinical trial. Sixty-three healthy women in their early menopause were randomized to treatment with bendroflumethiazide 5 mg/day or placebo for 2 yr, while both groups received placebo for the third year of the trial. Calcium supplement 0.5 g/day was given throughout the 36 mo to all participants. Bone mineral content (BMC) determined by 125I-photon absorptiometry of the forearms decreased 2% per year in the placebo group (p less than 0.001). In the thiazide group no fall in BMC was seen during the first 6 mo. whereafter BMC declined with the same rats as in the placebo group. At the end of the 3 yr trial BMC averaged 94.1% in the placebo group and 95.2% in the thiazide group (p greater than 0.05). Despite a daily supplement of 0.5 g calcium, thiazide induced a persistent fall in the urinary calcium excretion of 25% (p less than 0.001), whereas the calcium supplement in the placebo group caused a significant increase in mean urine calcium of 10%-20% (p less than .001). At stop of thiazide medication a rebound effect caused a marked rise in urine calcium. One month after withdrawal of the calcium supplement the urinary calcium excretion had returned to the initial level in both groups. It is concluded that despite a sustained urine calcium lowering action the effect of thiazide upon postmenopausal bone loss is shortlived.

Fracture frequency and bone preservation in postmenopausal women treated with estrogen.

Two hundred eighty-five normal 70-year-old Danish women were divided according to postmenopausal use of gonadal hormones into 3 groups: 1 virtually untreated (3 months or less, N = 231), 1 treated over a short term (4 months to 6 years, N = 36), and 1 treated over a long term (6 years or more, N = 18). The 3 groups had been treated for a median of 0, 6, and 70%, respectively, of their postmenopausal years. The degree of bone loss varied inversely with the duration of postmenopausal hormone treatment. Bone mineral content was 11.8% higher in the long-term treated group than in the untreated group (P less than .05). Likewise, the metacarpal bone mass was 8.5% greater (P less than .01). The number of women with postmenopausal fractures was 13% lower in the long-term treated group than in the untreated group (Difference not significant). Data from this retrospective study present evidence that estrogen protects bones in elderly women.

Validity in diagnosing osteoporosis. Observer variation in interpreting spinal radiographs.

Observer variation in interpreting radiograph of the spine in 70-year-old Danish women has been examined. The women joined a general health investigation as part of an epidemiologic screening for osteoporosis. Two experienced radiologists examined independently 280 sets of lateral radiographs of the spine to disclose fractures. The radiographs were examined four times, each examined at two different occasions by each radiologist. Overall intra-observer agreement was 88% and 87% when asked for presence or absence of fractures, irrespective of fracture localization. When accidental occurrence of agreement was taken into account (kappa analysis) intra-observer variation was reduced to 64% and 62%. The overall inter-observer agreement was 75%, but reduced to 47% when accidental occurrence of agreement was noted. Kappa analysis in testing observer variation indicates that a considerable part of agreement can be ascribed to chance alone. This seriously questions the hitherto used definition of osteoporosis.

Radiographic technique in the diagnosis of renal stones. A comparison of tomography and oblique projections.

Renal calcifications were disclosed equally well in 93 patients by oblique radiographs and tomograms evaluated independently by two radiologists. Bowel content influenced sensitivity and specificity of both methods to the same extent. Oblique projections are therefore recommended as screening procedure for renal calcifications.

Gender, lifestyles, and victimization: beyond routine activity.

Using data from a national survey of high school seniors and a study of high school students in Tucson, Arizona, this paper tests hypotheses about gender, routine activities, and delinquent activities as correlates of teenage victimization. The results are consistent with the hypotheses and suggest the following generalizations: (1) activities which involve the mutual pursuit of fun are more victimogenic than activities which passively put people at risk; (2) delinquent activity is positively related to victimization; (3) delinquent activity is more strongly related to victimization than nondelinquent activities; and (4) gender differences in victimization are reduced considerably by controls for delinquent activity. While offense activity cannot be demonstrated to precede victimization using cross-sectional data, the results do demonstrate the potential importance of delinquent activity in explanations of victimization among youths.

[AIDS in Denmark. 1. Opportunistic infections and malignant diseases. Danish Study Group for HIV infection]. / AIDS i Danmark. 1. Opportunistiske infektioner og maligne sygdomme. Danish Study Group for HIV Infection.

To examine the distribution of AIDS-defining illnesses among Danish AIDS patients, data on 687 AIDS patients diagnosed in the period from 1980 to 1990 (93% of all reported cases in the period) were collected. The most frequent AIDS-defining illness was Pneumocystis carinii pneumonia followed by candida oesophagitis and Kaposis sarcoma. The proportion of homo/bisexual men presenting with Kaposis sarcoma as the initial AIDS-defining illness declined over time. Patients with extrapulmonary tuberculosis had higher CD4 cell counts than patients presenting with other illnesses. Cytomegalovirus chorioretinitis and atypical mycobacteriosis were seen more frequently after the time of the AIDS diagnosis, and a low CD4 cell count at time of the AIDS diagnosis was a significant predictor for the development of these opportunistic infections during follow-up. Danish AIDS patients present with a wide spectrum of HIV-related illnesses, reflecting their exposure to opportunistic microorganisms and the degree of immune deficiency. The pattern of HIV-related illnesses is changing over time, and therefore continuous surveillance is needed to optimize therapeutic and prophylactic regimens.

[AIDS in Denmark. 2. Survival after the diagnosis of AIDS. Danish Study Group for HIV infection]. / AIDS i Danmark. 2. Overlevelse efter AIDS-diagnosen. Danish Study Group for HIV Infection.

The survival pattern was studied for 687 Danish AIDS patients (93% of notified cases in the study period) who were diagnosed with AIDS during the period from 1980 to 1990. The median survival was 17 months. Factors significantly associated with a shortened survival were transfusion-acquired HIV infection, age > 40 years, year of diagnosis before 1987, and the presence of either disseminated infection with Mycobacterium avium-complex, Cytomegalovirus chorioretinitis or malignant lymphoma at time of the AIDS diagnosis. There was also a significant association between survival and CD4 cell count at time of AIDS diagnosis. Patients who had CD4 cell counts above 200 x 10(6)/l had twice as long a survival as patients who had CD4 cell counts less than 50 x 10(6)/l. The prognosis of Danish AIDS patients remains poor. The most important determinant of survival time appears to be the degree of immune deficiency at time of diagnosis.

Osteoporosis of the slender smoker revisited by epidemiologic approach.

A representative sample of 285 70-year-old Danish women were examined by case history, 125I photon absorptiometry of both forearms (BMC), and lateral X-rays of the spine. Fat mass was calculated from height (H), weight (W) and estimated lean body mass (LBM) as W-LBM/H kg m-1. Seventy-five participants with previous or present disease or treatment known to influence the calcium metabolism were excluded. The remaining 210 women included the final study groups of seventy-seven long-term smokers and 103 non-smokers. Within both groups BMC correlated positively to fat mass, r = 0.447 and 0.560, respectively (P less than 0.001). The slopes of the regression lines and their positions were similar (P greater than 0.05). Hence, for a certain degree of overweight smoking per se does not influence BMC to a significant degree. Although the smokers were less obese (P less than 0.005) and tended to have lower BMC (P less than 0.10) their frequency of non-violent post-menopausal fractures, 40.3%, was the same as for non-smokers, 44.7%. The respective frequencies of definite osteoporotic fractures (i.e., spinal crush and fractures of the hip, proximal humerus and distal forearm) were comparable as well. In conclusion, the influence of smoking on the female skeleton seems mainly to be caused by the associated slenderness.

Does 1,25(OH)2D3 accelerate spinal bone loss? A controlled therapeutic trial in 70-year-old women.

The progress of spinal bone loss was monitored by measurements of the vertebral body height of T6 to L5 in seventy 70-year-old women who participated in a controlled, double-blind therapeutic trial. They were treated for one year by 1,25(OH)2D3, 0.50 micrograms a day (or less if hypercalcemia occurred) and cyclical estrogen/gestagen, alone or combined, or placebo. Sufficient calcium intake was ensured in all. The vertebral body height decreased significantly, by 1%, in both of the 1,25(OH)2D3 groups, whereas it remained unchanged in the hormone and the placebo + calcium group. This observation does not encourage the use of 1,25(OH)2D3 for prevention or treatment of postmenopausal bone loss.

Treatment of post menopausal osteoporosis. A controlled therapeutic trial comparing oestrogen/gestagen, 1,25-dihydroxy-vitamin D3 and calcium.

A controlled therapeutic trial on seventy-four 70-year-old women was carried out with the purpose of finding the optimal treatment for post menopausal osteoporosis. The bone mineral content (BMC) was measured by I-photonabsorptiometry at two sites in the distal part of the forearms, where the trabecular/cortical ratio is 0.25 and 1.5, respectively. Radiographs were done on the right hand to measure the metacarpal bone mass (cortical area/total area=CA/TA. After observing the spontaneous course of bone loss for 6 months the participants were allocated at random to 12 months' treatment with 1,25-dihydroxycholecalciferol [1,25(OH)2D3] and oestrogen/gestagen, alone or in combination, and calcium. The groups treated with oestrogen/gestagen [with or without 1,25(OH)2D3] showed a highly significant increase in BMC. In contrast bone mineral remained unchanged or decreased in both the calcium and the 1,25(OH)2D3 groups with a tendency towards more pronounced negative bone balance in the 1,25-(OH)2D3 group. Seven out of nineteen patients of 1,25(OH)2D3 developed hypercalcaemia, which necessitated a reduction in dosage. It is concluded that the new vitamin D metabolite, 1,25(OH)2D3, given in clinically acceptable doses, is without value in the treatment of post menopausal osteoporosis.

1,25(OH)2D3 and renal function. A controlled clinical study in normal elderly women.

A controlled study of the effect of 1,25(OH)2D3 was performed in 58 normal 70-year-old Danish women. After 6 months; observation of the spontaneous course the participants were randomized to treatment with either 1,25(OH)2D3 (0.5 micrograms daily) or placebo. Both groups received 500 mg calcium daily. Seven out of 20 participants treated with 1,25(OH)2D3 developed slight hypercalcaemia which disappeared after dose adjustment. One participant in the placebo group developed slight hypercalcaemia. A highly significant increase in serum creatinine was observed in the 1,25(OH)2D3 group when compared with the initial value and with the change in the placebo group. Serum creatinine remained elevated throughout the study despite normalization of serum calcium. It is concluded that 1,25(OH)2D3 treatment in normal, elderly women has a negative effect on the renal function as estimated from serum creatinine.

Urinary 99m-Tc-diphosphonate excretion as a simple method to quantify bone metabolism.

Twenty-four-hour whole-body retention (WBR) of 99m-Tc-methylene-diphosphonate (an index of bone turnover) was determined by whole-body counting (WBRs) and complementarily by urine counting (WBRu) in nineteen subjects with normal to highly increased bone turnover. WBRs and WBRu correlated well (r = 0.94, P less than 0.001), and gave almost the same results. Both WBRs correlated equally well with serum alkaline phosphatase and urine hydroxyproline/creatinine (r = 0.82-0.93). Coefficient of variation in WBRu was 7.0%, determined by duplicate measurements in sixteen normals. The injected dose of diphosphonate did not influence WBRu. However, since almost 50% of the diphosphonate excreted in urine appeared during the first few hours after the i.v. injection, the method of WBRu requires careful urine collection. Thus, the simple WBRu determination provides the same information on bone metabolism as does the more cumbersome and expensive WBRs technique.

Bone mass as referent for urinary hydroxyproline excretion: age and sex-related changes in 125 normals and in primary hyperparathyroidism.

Fasting urinary hydroxyproline: creatinine ratio (OHPr:Cr) and bone mineral content of the forearm (BMC) were measured in 125 normals, 67 females and 58 males, aged 20-79 years, and in 15 patients with primary hyperparathyroidism. In normals, both variables were significantly correlated to age and sex. The interrelation of OHPr:Cr and BMC was studied in subgroups of normals who were supposedly in metabolic balance, that is, females aged 20-39 years (n = 24) and males aged 20-49 years (n = 29). In both sexes OHPr:Cr and BMC were positively correlated: r = 0.60 and 0.58, respectively (P less than 0.001). On this basis, BMC correction of all OHPr:Cr values was undertaken now revealing a stable increased level of bone resorption per unit of bone mass in postmenopausal females. In males OHPr:Cr per unit of BMC remained unaltered throughout life. In primary hyperparathyroidism, in which increased bone resorption is inherent, the discriminatory power of OHPr:Cr was significantly improved when calculated per unit of BMC (P less than 0.001). These observations suggest that estimation of bone resorption by use of OHPr:Cr requires adjustment for differences in bone mass.