Wolfgang Woloszczuk

Serum levels of osteoprotegerin increase with age in a healthy adult population

Regulation of the balance of osteoblastic and osteoclastic activity is critical for the understanding of normal cell biology and forms the basis of metabolic bone diseases. Our study reports about influences of age and gender on serum levels of osteoprotegerin (OPG) and its association to other clinical parameters of bone metabolism in a precisely determined cohort of 1134 healthy subjects at 17 Austrian outpatient bone clinics, aged between 19 and 96 years (females n = 687, 50 +/- 21 years, 19-94, and males n = 447, 52 +/- 13.5 years, 24-96). Mean OPG serum levels for all participants were 50.83 +/- 51.47 pg/ml (n = 1134; median 36, 2-584) and we observed a sharp increase in females after 60 years and in males after 70 years of age. OPG serum levels increased significantly by age, 2.1 pg/ml in females and 1.9 pg/ml in males for every year (P < 0.0001). Correlation of OPG serum levels and several bone parameters of bone metabolism showed that OPG negatively correlated with serum iPTH (r = -0.14; P < 0.001) and with serum estradiol in females (r = -0.16, P < 0.0001). Bone mineral density measured by DXA method at the spine and at the hip did not correlate with OPG serum levels, except a borderline negative correlation at the trochanteric region (r = -0.1, P < 0.05) in females only. Our results show a significant increase of osteoprotegerin with age in healthy females and males but fluctuations do not predict bone mineral density under in vivo conditions.

Primary hyperparathyroidism: Incidence of cardiac abnormalities and partial reversibility after successful parathyroidectomy

PURPOSE This prospective study was designed to assess the effect of primary hyperparathyroidism on heart muscle, valves, and myocardial function. Echocardiography was used to evaluate changes in mechanical performance, the thickness of the left ventricular wall, myocardial calcific deposits, and valvular calcifications in patients with primary hyperparathyroidism. METHODS Echocardiography was performed in 54 patients with hyperparathyroidism prior to surgery and 12 +/- 2 months after successful parathyroidectomy. A matched control group was followed for comparison. RESULTS In a blinded fashion, aortic and mitral valve calcifications were detected in 63% and 49% of patients with primary hyperparathyroidism (controls: 12% and 15%, respectively). Calcific deposits in the myocardium were found in 69% of patients with hyperparathyroidism and 17% of the control subjects. After parathyroidectomy and 12 months of normocalcemia, a significant regression of left ventricular hypertrophy (p < 0.001) was observed. CONCLUSIONS The present data show a high incidence of left ventricular hypertrophy, calcific deposits in the myocardium, and/or aortic and mitral valve calcification in patients with primary hyperparathyroidism. A 1-year follow-up after parathyroidectomy (and restoration of normocalcemia) discloses regression of hypertrophy, while calcifications persist without evidence of progression.

Assessment of vitamin D and calcium status in healthy adult Austrians

Background Because there is reason to assume that also in Austria calcium and vitamin D malnutrition is wide‐spread, we initiated a comprehensive study on calcium and vitamin D status in relation to bone health in a large group of the normal adult population.

Value of cardiopulmonary exercise testing and big endothelin plasma levels to predict short-term prognosis of patients with chronic heart failure.

OBJECTIVES We tested the hypothesis that, in patients with stable heart failure, measuring big endothelin-1 (ET-1) plasma level at rest predicts short-term prognosis better than peak oxygen consumption (VO2max) at exercise. BACKGROUND Cardiopulmonary exercise testing and evaluation of neurohumoral plasma factors are established tools to estimate survival in patients with heart failure. No data, however, exist comparing the prognostic value of both marker categories simultaneously. METHODS Two hundred twenty-six heart failure patients were studied in regard to a combined end point of death and prioritization for urgent cardiac transplantation within 1 year follow-up. RESULTS During the study period 149 patients were without cardiac events (group A), 69 patients died or were urgently transplanted (group B) and 8 patients were alive after a nonurgent heart transplant operation. Norepinephrine (p < 0.0001), atrial natriuretic peptide (p < 0.001), big endothelin plasma levels (p < 0.0001 as well as workload, VO2max and achieved percentage of predicted peak oxygen consumption (pVO2max) (all p < 0.0001) differed significantly between groups A and B. In multivariate stepwise regression analysis, however, only big ET-1 plasma concentration (chi2=74.4, p < 0.0001), New York Heart Association function class (chi2=33.9, p < 0.0001), maximal workload (chi2=7.2, p < 0.01, and plasma atrial natriuretic peptide (ANP) concentration (chi2=4.6, p < 0.05) were independently related to outcome. Peak oxygen consumption or pVO2max did not reach statistical significance in this model. Event-free survival rates were significantly lower in patients with a big ET-1 level of 4.3 fmol/ml or more than with lower big ET-1 levels (p < 0.0001). CONCLUSION We conclude that in patients with chronic heart failure who are stable on oral therapy measuring big ET-1 and ANP plasma levels may be a valuable noninvasive adjunct to improve the prognostic accuracy of detecting high risk patients compared with exercise testing alone.

The effect of age and gender on cytokine production by human peripheral blood mononuclear cells and markers of bone metabolism

BACKGROUND Aging has been associated with various alterations of immune functions, the musculoskeletal system and a decline of sex hormone levels. Estradiol has a central role in the regulation of bone turnover and also modulates the production of cytokines such as interleukin-1 and -6 and tumor necrosis factor-alpha. We therefore studied the effect of age and gender on cytokine production by mononuclear cells and markers of bone metabolism. METHODS Peripheral blood mononuclear cells were isolated from young and elderly subjects; intracellular detection of cytokine production after stimulation with ionomycine and PMA (T cells) or LPS (monocytes) was performed by four color flow cytometry. Sex hormone levels and markers of bone metabolism were measured by RIA or ELISA: RESULTS When we compared elderly to young women we found an increased proportion of T cells that were positive for interferon-gamma, interleukin-2, -4, -10 and -13. Also the percentage of cells producing interleukin-4 or interferon-gamma within the CD8(+) population was higher in the group of elderly women. In contrast, proportionally fewer monocytes of elderly women were positive for tumor necrosis factor-alpha or interleukin-6 than those of young women. In elderly men a higher percentage of T cells produced interleukin-2, -4 and -13. In the group of aged men we found a higher frequency of cells that produced interleukin-4 within the CD4(+) or CD8(+) population. Moreover, within monocytes of elderly men we found an increased percentage of cells positive for both interleukin-1beta and tumor necrosis factor-alpha. The data on markers of bone metabolism indicated an increase of bone turnover in old age. CONCLUSION Our data demonstrate that aging is associated with significant alterations of bone metabolism and cytokine production by T cells and monocytes. For particular cytokines (interferon-gamma and interleukin-10 in T cells, interleukin-6 and tumor necrosis factor-alpha in monocytes) these changes are gender specific.

Relationship between neopterin and granulocyte elastase plasma levels and the severity of multiple organ failure

In a series of 56 patients (24 uncomplicated postoperative and 32 septic patients), neopterin and elastase alpha 1 protease inhibitor complex (E-alpha 1 PI) plasma levels were measured daily. The clinical course of each patient was evaluated with the Multiple Organ Failure (MOF) score according to Goris. Neopterin could differentiate between septic and nonseptic patients (p less than .001), and E-alpha 1 PI between septic nonsurvivors and nonseptic patients only (p less than .01). In septic patients, acute pulmonary insufficiency was indicated by elevated E-alpha 1 PI values (greater than or equal to 400 micrograms/L) 1 day before mechanical ventilation was performed with a sensitivity of 81% and a specificity of 82%. Defining a patient with MOF whose score was greater than or equal to 5 as a high-risk septic patient, a comparison neopterin greater than or equal to 40 nmol/L and E-alpha 1 PI greater than or equal to 400 micrograms/L, measured 1 day before the evaluation of an MOF score of greater than or equal to 5 yielded a sensitivity of 91% and a specificity of 99% when patients fulfilled both criteria. We conclude that neopterin and E-alpha 1 PI might be useful parameters for the diagnosis of septicemia and monitoring of the clinical course in septic patients. Moreover, they might indicate the possible central role of macrophage and PMN activation in the development of MOF.

Bone mineral density and biochemical parameters of bone metabolism in female patients with systemic lupus erythematosus

OBJECTIVE To evaluate bone mineral density and biochemical parameters of bone metabolism in ambulatory premenopausal female patients with systemic lupus erythematosus (SLE). METHODS 30 women who fulfilled the ARA criteria for the classification of SLE were studied. Lumbar and femoral bone mineral density was determined by dual energyx ray absorptiometry. Various laboratory parameters including serum calcium, serum phosphorus, alkaline phosphatase, bone specific isoform of alkaline phophatase, propeptide of type 1 procollagen, deoxypyridinoline excretion, telopeptide of type 1 collagen, serum creatinine, osteocalcin, parathyroid hormone, 25-OH vitamin D, testosterone, progesterone, estradiol, follicle stimulating hormone and luteinotropic hormone were measured. RESULTS According to the WHO criteria 39% of all patients with SLE studied had normal bone mineral density, 46% had osteopenia and 15% had osteoporosis at the lumbar spine; at the femoral neck 38.5% had normal bone mineral density, 38.5% had osteopenia and 23% suffered from osteoporosis. Significantly lower osteocalcin levels were found in SLE patients. All other bone resorption and formation markers measured were not statistically different, but higher serum albumin corrected calcium and lower phosphorus values were found in the SLE group. Of all sex hormones tested lower testosterone and higher follicle stimulating hormone concentrations were seen in patients with SLE. CONCLUSION A high incidence was found of osteopenia and osteoporosis in premenopausal patients with SLE. Bone diminution in SLE seems to be attributable, at least in part, to decreased bone formation in SLE patients.

Bone mass and biochemical parameters of bone metabolism in men with spinal osteoporosis

Abstract. With advancing age both sexes have an increased incidence of osteoporotic fractures, although fractures are more common in women than in men. Whereas in women several potential risk factors have been identified, less is known about osteoporosis in men. A total of 27 Austrian men (mean age: 65 ± 2 years) with atraumatic spine fractures were studied. In all patients, medical history gave no evidence of disease or medications causing osteoporosis. Peripheral bone mass was determined by single‐photonabsorptiometry on the distal non‐dominant forearm; lumbal bone density was measured by quantitative computed tomography. Serum levels of calcium, phosphate, alkaline phosphatase, osteocalcin, testosterone, estrogen, parathyroid hormone and 25‐hy‐droxy‐vitamin D as well as 2‐h‐urinary‐OH proline and calcium excretion were measured. All data were compared with those of an age and sex matched control group consisting of 19 healthy males. A significant difference in mean peripheral and axial bone mass (SPA: P<0.004; QCT: (P<0.001) was observed between osteoporotic men and controls. When compared to controls, serum levels of alkaline phosphatase (P<0.012), urinary OH proline (P<0.05) and urinary calcium excretion (P<0.003) were significantly higher in the osteoporotic males. Additionally, there was a significant positive correlation between serum alkaline phosphatase and urinary OH proline excretion (r=0.32; P<0.04) in the osteo‐porotics. All other biochemical parameters showed no significant differences. Our results may lead to the assumption that osteopenia in men is related to increased bone turnover.

Bone turnover markers and sex hormones in men with idiopathic osteoporosis.

Background In contrast to osteoporosis in postmenopausal women, osteoporosis in men has received much less attention.

Osteoprotegerin and the receptor activator of NF-kappa B ligand in the serum and synovial fluid. A comparison of patients with longstanding rheumatoid arthritis and osteoarthritis

We examined OPG and soluble RANKL in the serum (sOPG, sRANKL) and synovial fluid (synOPG, synRANKL) in patients with rheumatoid arthritis (RA) and osteoarthritis (OA). OPG and RANKL were measured in 85 patients (44 with RA, 41 patients with OA) in serum and synovial fluid as well. For measuring of OPG and RANKL ELISA tests were used. The results of OPG and RANKL were compared with clinical and radiological scores. We found a negative correlation for OPG and RANKL in synovial fluids: not only for the whole group of patients (P< 0.003, r=−0.32), but also for the subgroups (RA: P<0.04, r=−0.28, OA: P<0.002, r=−0.54). SRANKL and synRANKL were positively correlated in the whole group (P<0.01, r=0.25) and in the OA group (P<0.02, r=0.35); the RA group was showing a trend (P<0.063, r=0.24), however. Serum OPG was lower in RA, synOPG higher in OA. The difference between the two patient groups was only significant for synOPG (P<0.03, r=0.056), but not for sOPG (P<0.09, r=0.19), sRANKL (P<0.43, r=0.85) or synRANKL (P<0.11, r=0.22). The synOPG:synRANKL ratio was significantly correlated with the Larsen score (P<0.004, r=0.38). Synovial OPG is significantly decreased in rheumatoid joints, whereby synovial RANKL is increased. Lower synOPG could reflect a lower protective effect on bone, thus leading to an earlier and more pronounced bone destruction in RA. However, the effect of different mediators for joint destruction in RA and OA seems not to be important to the pathophysiological changes in the joints. The upregulation of serum OPG might be the result of the inflammation; in contrast, an upregulation of RANKL could not be found in the serum of patients with RA and OA.