Changes in weight, fluid balance and serum albumin in patients referred for nutritional support.

BACKGROUND AND AIMS: Starvation and injury impair the excretion of an excess sodium and water load, resulting in oedema and hypoalbuminaemia, which may have adverse effects on gastrointestinal physiology. We have retrospectively assessed clinical signs and fluid balance in 44 adult patients referred for nutritional support for >== 10 days. METHODS: Clinical evidence of oedema was noted. Oedematous patients were managed with a low sodium (0-50 mmol/day), low volume (2 l/day) feed. Some also received albumin and a diuretic. Body weight was recorded daily and serum albumin three times weekly. The lowest recorded weight during nutritional support and the weight at the time of discharge were correlated with serum albumin concentration. RESULTS: The 21 patients with oedema had acute surgical conditions and complications such as sepsis while the 23 non-oedematous patients had chronic conditions with gradual nutritional depletion. During nutritional support the mean (SEM) weight in kg of the oedematous patients fell from 79.3 (2.9) to 69.2 (3.2) (P>> 0.00001) and subsequently rose to 70.1 (3.2) (P= 0.005). Corresponding values for the non-oedematous patients were 61.4 (4.0), 60.2 (3.9) (P>> 0.05) and 61.2 (3.7) (P= 0.002) respectively. Weight reduction reflected negative salt and water balance and correlated with a rise in serum albumin (r = -0.61 for oedematous and r = -0.65 for non-oedematous patients) largely reflecting reversal of previous dilution. CONCLUSION: These findings have important implications for the salt and water content of perioperative fluid and nutritional prescriptions. They also emphasize the dilutional component of hypoalbuminaemia in these patients.

Adverse endometrial effects during long cycle hormone replacement therapy. Scandinavian Long Cycle Study Group.

OBJECTIVES: Treatment with unopposed estrogen is known to increase the risk of endometrial hyperplasia, atypia, and carcinoma, and therefore the administration of a progestin during hormone replacement therapy (HRT) is recommended. The addition of a progestin may cause unwanted side effects. Progestin administration of various durations are therefore used in HRT. STUDY DESIGN: Data were obtained about endometrial histopathology, bleeding interval and compliance in 240 early postmenopausal women receiving HRT with a progestin administered for 10 days during 12 week or 4 week cycles of estrogen administration. These regimens were studied for as long as 4 years. The daily estrogen given was 17beta-estradiol 2 mg per day which was reduced to 1 mg day during the last 6 days of each cycle. The progestin used was norethindrone acetate, given at a dose of 1 mg per day. RESULTS: The incidence of endometrial hyperplastic changes, i.e. simple or complex hyperplasia, atypia or cancer, was significantly higher in the 12 weeks cycle than in the monthly cycle group (P = 0.003), with an overall annual incidence of 5.6% in the 12 weeks cycle group and 1% in the monthly cycle group. One case of atypical hyperplasia and one case of endometrial adenocarcinoma was observed in the long cycle group. Long cycle treatment produced more irregular bleeding pattern. Accordingly, the rate of drop-out due to bleeding was significantly higher in the long cycle group (P<0.01). CONCLUSION: We conclude that the long cycle HRT modality investigated did not improve compliance and may increase the risk of endometrial hyperplasia and eventually cancer compared to conventional HRT with a monthly cycle. Caution using long cycle HRT regimens is advisable, and careful monitoring of the endometrium during treatment is recommended.

Tibolone: influence on markers of cardiovascular disease.

Tibolone, a synthetic steroid with estrogenic, androgenic, and progestogenic properties relieves climacteric symptoms and prevents postmenopausal bone loss. The influence of tibolone treatment on coagulation, fibrinolysis, and lipid metabolism was investigated in 91 healthy late postmenopausal women. They were randomly assigned in a double-blind, placebo-controlled 2-year study to receive either tibolone 1.25 mg (n = 36, 29 completed) or 2.5 mg (n = 35, 28 completed) or placebo (n = 20, 13 completed). The biochemical markers of lipid metabolism, fibrinolysis, and coagulation were measured every 3 months. In both tibolone groups a similar (approximately 30%) decrease in high density lipoprotein cholesterol and a corresponding lowering of apolipoprotein A-1 (P < 0.001) was detected. Also serum total cholesterol and triglycerides were reduced (approximately 15%; P < 0.01), whereas low density lipoprotein cholesterol, apolipoprotein B, and lipoprotein(a) were unaffected by tibolone. The two dose levels of tibolone resulted in a similar, marked lowering (approximately 30%) of tissue plasminogen activator and plasminogen activator inhibitor activity as compared with placebo (P < 0.001). Plasminogen increased (approximately 15%; P < 0.001) in both groups. Fibrinogen was lowered (P < 0.01) in the low-dose group, and antithrombin III remained unchanged. The overall effect on hemostatic factors of the present doses of tibolone in healthy, late postmenopausal women tends towards increased fibrinolysis and unchanged coagulation. This may be beneficial and might theoretically counterbalance the potentially negative effect of the decrease in high density lipoprotein cholesterol.

The response in spinal bone mass to tibolone treatment is related to bone turnover in elderly women.

To determine the ability of bone turnover to predict the response in bone mass during treatment with Tibolone, two biochemical markers of bone metabolism were evaluated [CrossLaps corrected for urinary creatinine (CrossLaps/Cr.) and serum osteocalcin measured in a newly developed assay (N-Mid)]. Data from a 2-year double-blind, randomized trial with 56 completing Tibolone-treated women and 13 placebo-treated women were studied. Bone mineral density in the spine (QDR-1000) and indices of bone turnover were determined every 3 months throughout the study. The response in bone mass was calculated as the percent annual change in bone mineral density from baseline and was determined from a total of nine measurements. The response in bone mass was correlated to prestudy values of CrossLaps/Cr. (r = 0.27; p < 0.05), but was uncorrelated to prestudy values of N-Mid. The changes from baseline of these two markers were significantly correlated with the response in bone mass from the 6 months' time point and throughout the rest of the study, i.e., at 1 year: CrossLaps/Cr.: r = 0.54; p < 0.001, N-Mid: r = 0.49; p < 0.001). The change from baseline in the two markers was clearly more predictive of the response in bone mass than the baseline values of these markers as evaluated in a multiple, linear regression-model. Within 1 year of Tibolone-treatment, measured changes in CrossLaps/Cr. and bone mineral density are at least equally predictive of the true response in bone mass over 2 years. These results indicate a possibility of monitoring Tibolone therapy with biochemical markers of bone turnover, at least on group basis.

Tibolone: prevention of bone loss in late postmenopausal women.

The aim of the study was to assess the effects of 2 yr of treatment with two dose levels of tibolone on bone mineral density and bio-chemical markers of bone metabolism in late postmenopause. Ninety-one healthy women, more than 10 yr after menopause, entered a 2-yr double blind, randomized, placebo-controlled study of treatment with either 1.25 mg/day (n = 36) or 2.5 mg/day (n = 35) Tibolone or placebo (n = 20). Densitometry and determinations of biochemical markers of bone metabolism in serum and urine were performed before randomization and every 3 months during the study. The results revealed a steady and equal increase in bone mineral density in both tibolone groups at the bone sites studied. Gains in BMD spine of 5.9 +/- 0.9% in the 1.25 mg group, 5.1 +/- 0.9% in the 2.5 mg group, and 0.4 +/- 1.1% in the placebo group were found. In the forearm, increases of 2.2 +/- 0.7% in the 1.25 mg group and 1.9 +/- 1.1% in the 2.5 mg group were detected, whereas the placebo group lost 2.1 +/- 1.0%. This was fully supported by changes in biochemical markers of bone resorption (urinary excretion of fragments from the osteoclastic degradation of the alpha 1-chain of the C telopeptides of type 1 collagen and hydroxyproline) and bone formation (serum osteocalcin), respectively. In conclusion, within 2 yr of treatment, tibolone increases bone mass in the spine and prevents bone loss in the forearm in late postmenopausal women determined by densitometry and several biochemical parameters of bone turnover. Tibolone at two doses (1.25 and 2.5 mg/day) had similar effects, indicating that even lower doses may be efficacious.

Anteroposterior and lateral spinal DXA for the assessment of vertebral body strength: comparison with hip and forearm measurement.

Spinal bone mineral density (BMD) is traditionally measured by dual-energy X-ray absorptiometry (DXA) in the anteroposterior (AP) projection which includes both the vertebral body and the posterior elements in the measurement. The posterior elements, however, contribute little to the compressive strength of the spine. It has therefore been suggested that spinal BMD measured in the lateral projection, including only the vertebral body in the measurement, might be more appropriate for the prediction of fracture risk. To date little clinical evidence has been presented to support this assumption. To address the issue, we measured vertebral, hip and forearm BMD in situ in 14 human cadavers and remeasured BMD in vitro in excised vertebrae. Lateral spinal measurements were performed in the decubitus position. Fracture force and other biomechanical measures were determined for 32 vertebrae in a mechanical testing machine and compared with BMD values in situ and in vitro. Correlations of BMD with vertebral fracture force were r = 0.48/0.51 (in situ/in vitro) for the AP spinal measurements, r = 0.45/0.71 (in situ/in vitro) for the lateral spinal measurements, and r = 0.64 and r = 0.53 for total hip and forearm measurements in situ, respectively. Thus, despite an apparent diagnostic advantage in vitro, lateral spinal BMD measurement was not superior to AP measurement when performed in situ. This observation corresponds well with previous clinical findings and is probably due to the larger accuracy error in the lateral than in the AP projection resulting from a lower ratio of bone to soft tissue. The high correlation between hip BMD and vertebral fracture force suggests that hip measurement may prove as useful for vertebral fracture risk assessment as spinal measurement in any projection, especially in the elderly with a high prevalence of degenerative changes in the spine.

Dual energy X-ray absorptiometry of the spine--decubitus lateral versus anteroposterior projection in osteoporotic women: comparison to single energy X-ray absorptiometry of the forearm.

We investigated the discriminatory ability of dual energy X-ray absorptiometry (DXA) of the lumbar spine in the anteroposterior vs. decubitus lateral projection in 53 elderly women with at least one vertebral fracture and 63 age-matched women without fracture. Twenty-three premenopausal healthy women served as a reference group. Spine measurements were compared to forearm measurements by single energy X-ray absorptiometry (SXA). Bone mineral density (BMD) of the women with fractures was 16% lower in the AP projection and 17% lower in the decubitus lateral projection compared to age-matched women without fractures. t-Scores (deviation from normal premenopausal values in SDs) were -2.1 to -2.3 in the women without fractures, and -3.9 (AP projection), -3.1 (lateral projection) and -3.8 (forearm) in the women with vertebral fractures. t-Scores as well as z-scores for bone mineral content of the vertebral body and the vertebral posterior elements (both measured with the lateral projection) were similar. ROC analysis showed no significant difference between the AP and the lateral projection of the spine. When subjects with vertebral endplate sclerosis (about 25% in each group, with considerably elevated spinal BMD) were excluded, it did not significantly change the diagnostic abilities for fractures. We found no diagnostic advantage of the lateral projection as compared to the AP projection or forearm measurement. Future studies will reveal whether absorptiometry in the lateral projection can be improved by supine lateral scanning.

Early postmenopausal diminution of forearm and spinal bone mineral density: a cross-sectional study.

Diminution of bone mineral density (BMD) in the spine and forearm was studied cross-sectionally in 363 women who were 6 months to 10 years postmenopausal. BMD was determined by dual-energy X-ray absorptiometry (DXA) (Hologic QDR-2000) in the lumbar spine, in both the supine lateral (LAT) and anteroposterior (AP) projections, and in the distal third of the forearm. The postmenopausal diminution of BMD was best described by an exponential fit. The initial rate of postmenopausal diminution of BMD was highest in the most trabecular sites (LAT > AP > forearm), but 10-year diminution was similar at all sites (12%-13%, corresponding to about 1.0-1.5 SD), and extrapolation suggested reverse order of the rates of diminution thereafter (forearm > AP > LAT). When bone mineral content of the entire L3 vertebra (tBMC) was measured in vivo, AP tBMC could account for only 67% of the variation in LAT tBMC, compared with r2 = 0.997 in vitro. This observation suggests an accuracy problem in vivo in one of the spine measurement methods. We conclude that the initial rate of BMD diminution after the menopause seems to be highest in the spine, especially when measured laterally, but that this rate levels off within the first decade. The lower precision error of a forearm measurement (0.8% v 1.6 for AP and 3.1 for LAT) therefore implies that this method may require a shorter observation period than spine measurements for the detection of bone loss 5-10 years after menopause. Long-term longitudinal spine and forearm measurements are, however, needed to confirm these conclusions.