What have we learnt about high-density lipoprotein cholesterol measurements during 32 years? Experiences in Finland 1980-2012.

BACKGROUND: High-density lipoprotein cholesterol (HDL-C) is important in risk assessment for cardiovascular disease or metabolic syndrome; however, different direct HDL-C assays may lead to erroneous risk estimates and potentially misclassify people. METHODS: Data for 30-year HDL-C trends in Finland were obtained from the national FINRISK surveys during 1982-2012 (n=45766) taking into account biases from three external quality assessment programs (EQA). We also compared two different direct HDL-C and turbidimetric apolipoprotein A-I methods using 413 fresh serum samples. RESULTS: HDL-C concentrations in the Finnish population were on average 1.33 (±0.04) mmol/l for men and 1.62 (±0.05) mmol/l for women after bias-correction. Positive HDL-C trends were observed for both sexes with original data, but trends disappeared after bias-correction. Comparison of two direct HDL-C methods demonstrated concentration-dependent difference. When HDL-C concentrations were <1.0 mmol/l, the mean bias was -12.0% (95% CI -13.5 to -10.0) whereas HDL-C concentrations >1.55 mmol/l showed mean bias of 9.0% (95% CI 7.0-10.5). CONCLUSIONS: Accurate reporting of HDL-C concentrations at the population level requires proper and regular attendance to reliable EQA programs. We found evidence for a concentration-dependent difference between some direct HDL-C methods, which may cause misclassification of people in cardiovascular risk assessment.

Serum tartrate-resistant acid phosphatase 5b in monitoring bisphosphonate treatment with clodronate: a comparison with urinary N-terminal telopeptide of type I collagen and serum type I procollagen amino-terminal propeptide.

Osteoclastic tartrate-resistant acid phosphatase activity in serum (S-TRACP 5b) was measured in postmenopausal women ( n =59, mean age 56.1 years) with vertebral osteopenia before and during 2-year treatment with an 800-mg daily dose of clodronate, with a non-amino bisphosphonate. Changes in TRACP 5b were compared with those in urinary excretion of type I collagen amino-terminal telopeptide (U-NTX), corrected for creatinine excretion, a well-established marker of bone resorption, and to serum type I procollagen amino-terminal propeptide (S-PINP), a marker of bone formation. Marker changes 1 year after start of treatment were correlated with changes in bone mineral density (BMD). The least significant change (LSC) for each marker and BMD was calculated from values for subjects receiving placebo. Responders to treatment were those exhibiting a change larger than LSC. In response to clodronate treatment S-TRACP 5b (mean change up to -18%) decreased less than did U-NTX (up to -51%) or S-PINP (up to -46%). Marker changes correlated with changes in lumbar spine and trochanter BMD. The most efficient marker for finding responders to treatment was S-PINP, which changed more than the LSC (32%) in 72% of the subjects at the 1-year time point and in 79% at the 2-year time point. S-TRACP 5b change exceeded the LSC (27%) in 40% and 34% of the subjects at each time point, while U-NTX change exceeded the LSC (55%) in 55% and 40%, respectively. We conclude that, in terms of the proportion of subjects exhibiting any change exceeding the LSC, S-TRACP 5b did not appear to be superior to U-NTX and S-PINP in the follow-up of clodronate treatment. The reason may lie in the mechanism of action of clodronate, which rather than reducing the number of TRACP 5b-secreting osteoclasts, reduces the activity of bone proteolytic enzymes and thus the rate of bone organic matrix degradation. This is seen in decreased amounts of type I collagen breakdown products (U-NTX), and through coupling of bone resorption with bone formation, in a decrease in circulating levels of the marker that reflects new collagen formation (S-PINP).

Clodronate as a single-dose intravenous infusion effectively provides short-term correction of malignant hypercalcemia.

The efficacy and safety of a single intravenous (I.V.) infusion of clodronate 1500 mg or 900 mg was compared with a single I.V. infusion of pamidronate 90 mg in the treatment of malignant hypercalcemia. Primary efficacy data from two separate, but parallel, randomized double-blind controlled multi-center studies (N = 63), involving patients with malignant hypercalcemia (S-Ca(cor) > 2.68 mmol/l), were pooled along with results from a study (N = 4), in which an open I.V. phase was followed by a randomized oral phase. The primary efficacy variable, the proportion of normocalcemic patients at day 5 could be evaluated from 51 subjects. Of them, 21 were in the clodronate 1500 mg group, 10 in the clodronate 900 mg group and 20 in the pamidronate 90 mg group. After the rehydration, the patients were given a single I.V. infusion of clodronate 1500 mg, clodronate 900 mg or pamidronate 90 mg. The patients were followed up for five days and S-Ca(cor) was measured daily. At day 5, a total of 16 patients (76%) in the clodronate 1500 mg group, six patients (60%) in the clodronate 900 mg group and 17 patients (85%) in the pamidronate 90 mg group were normocalcemic, the differences between the treatment groups being statistically non-significant. The differences in the mean S-Ca(cor) between the treatment groups were statistically non-significant. I.V. clodronate given either as 900 mg or 1500 mg single-dose was safe and well tolerated.

The effects of transdermal estrogen therapy on bone mass and turnover in early postmenopausal smokers: a prospective, controlled study.

OBJECTIVE: The purpose of this study was to investigate whether smoking reduces the effects of transdermal estrogen replacement therapy on bone. STUDY DESIGN: One hundred forty-eight women (0.5-5 years after menopause, aged 46-58 years) completed the study. Smokers were assigned randomly to receive either 1.0 mg (n=32 women) or 1.5 mg (n=31 women) of transdermal estradiol in gel daily, and nonsmokers (n=46 women) were assigned to receive 1.0 mg of transdermal estradiol for 2 years. The control group consisted of 17 smokers and 22 nonsmokers. Bone mineral density was measured by dual-energy x-ray absorptiometry. Bone turnover was assessed by measurements of urinary aminoterminal telopeptide of type I collagen and serum aminoterminal propeptide of type I procollagen. RESULTS: Lumbar spine bone mineral density increased similarly in smoking (+3.6%) and nonsmoking (+2.6%) estrogen users (P<.0001 to a decrease of 2.5% in the control group). Femoral neck bone mineral density increased 2.2% to 2.4% in smoking and nonsmoking estrogen users but decreased 0.2% in control subjects (P<.05). Urinary aminoterminal telopeptide of type I collagen decreased similarly in all estrogen-using groups (P<.05 to control group), but serum aminoterminal propeptide of type I procollagen decreased more in smoking than in nonsmoking estrogen users (P=.006). Serum 25-hydroxyvitamin D was 20% lower (P=.004) in smokers than in nonsmokers. CONCLUSION: Transdermal estrogen treatment protects smoking women as effectively as nonsmokers from osteoporosis. Smoking worsens the vitamin D state of postmenopausal women.