Quantitative ultrasound of bone and markers of bone turnover in Cushing's syndrome.

Quantitative ultrasound (QUS) of bone is a valuable tool in the assessment of postmenopausal osteoporosis. QUS and new markers of bone turnover have been poorly assessed in Cushing's syndrome, however. Twenty-five patients with Cushing's syndrome (20 women, 3 men; mean age +/- SEM: 38+/-2 years) were studied and compared with 35 age- and sex-matched control patients (mean age +/- SEM: 38+/-2 years). The following variables were measured in both groups: QUS parameters at the heel (BUA; SOS; Stiffness Index, SI); bone mineral density (BMD) at both the lumbar spine (LS) and femoral neck (FN) by dual-energy X-ray absorptiometry; and serum markers of bone turnover (osteocalcin, procollagen type I N- and C-terminal propeptides (PINP and PICP), bone alkaline phosphatase (BAP), procollagen type I C-terminal telopeptide (ICTP) and urinary type I collagen C-telopepetide breakdown products (CTX)). Both BUA and SI were decreased in patients with Cushing's syndrome (p<0.01) but not SOS (p=0.08). BMD was also strongly decreased in Cushing's syndrome, at both the LS and FN (p<0.005). The two markers of bone turnover statistically significantly different between the two groups were osteocalcin (mean + SEM: 3.5 + 0.7 ng/ml (Cushing's syndrome) vs 6.4+/-0.5 ng/ml (controls, p<0.01)) and CTX (mean +/- SEM: 148.7+/-17.1 microg/mmol Cr (Cushing's syndrome) vs 220.8+/-22.9 microg/mmol Cr (controls), p<0.05). The areas under the receiver operating characteristic curve (AUC) were 0.72 (BUA), 0.73 (SI), 0.90 (BMD(LS)), 0.81 (BMD(FN)), 0.83 (osteocalcin) and 0.64 (CTX) respectively. AUC was significantly higher for BMD(LS) than for both BUA and SI (p<0.05). Conversely AUC was not statistically significantly different for BMDFN as compared with either BUA or SI. AUC was also higher for osteocalcin than for other markers of bone turnover. In conclusion, QUS of bone seems to be a relevant tool for assessing bone involvement in Cushing's syndrome. QUS does have a lower sensitivity compared with DXA, however, and the relevance of QUS cannot be ascertained until some longitudinal data are forthcoming. Except for CTX, the other new markers of bone turnover assessed in this study (PINP, PICP, BAP and ICTP) do not seem of interest in Cushing's syndrome.

Bone ultrasonometry and turnover markers in primary hyperparathyroidism.

Quantitative ultrasound (QUS) of bone and new markers of bone remodeling have been poorly investigated in mild primary hyperparathyroidism (PHPT). In this study 26 patients (20 females and 6 males) were evaluated. BUA and SOS were measured by QUS at the heel. Markers of bone remodeling assessed were bone alkaline phosphatase (BAP), osteocalcin (OC), procollagen type I N- and C-terminal propeptides (PINP et PICP), and procollagen type I C-terminal telopeptide in blood and urine (ICTP and CTX). Bone mineral density (BMD) was measured at the lumbar spine (LS), femoral neck (FN), and Ward's triangle (WT). The control group comprised 35 sex- and age-matched subjects. The statistically significant variables between the two groups were (P < 0.05) BUA, BMD(LS), BMD(FN), BMD(WT), BAP, and OC. Corresponding z-scores were -0.55 +/- 0.75, -0.66 +/- 0.77, -0.66 +/- 0.71, -0.67 +/- 0.52, 1.87 +/- 3.87, and 1.93 +/- 3.53, respectively. Although PICP and PINP levels were higher in PHPT patients as compared with controls, the difference was not significant. Several markers of bone turnover were moderately correlated with both QUS (r = -0.39 to -0.55) and BMD (r = -0.48 to 0.63). In conclusion QUS seems to be a relevant tool in the assessment of bone status for patients with mild PHPT.

Causes of osteoporosis in males. A review of 160 cases.

BACKGROUND: The discovery of osteoporosis in a male requires a careful search for a cause. OBJECTIVE: To evaluate etiologic factors in male osteoporosis. PATIENTS AND METHODS: Males admitted to our department for osteoporosis were included if they had a nontrauma-related vertebral or peripheral fracture and/or a spinal or femoral neck bone mineral density value 2.5 standard deviations or more below the mean in young subjects. The study was retrospective from 1990 to 1995 and prospective from 1996 to 1997. During the prospective part of the study, each subject underwent a standardized battery of laboratory tests including renal tubular function parameters. Causes identified during these two periods were compared. RESULTS: Of the 160 patients included in the study, 28.1% had idiopathic osteoporosis, 22.5% had alcoholic osteoporosis, 19.4% had glucocorticoid-induced osteoporosis, 12.5% had osteoporosis due to moderate idiopathic proximal tubule dysfunction, and 8.8% had senile osteoporosis. The proportion of patients with idiopathic osteoporosis was 30% (23/76) during the retrospective part of the study and 26% (21/84) during the prospective part (nonsignificant difference). Moderate idiopathic proximal tubule dysfunction was found in 2.6% (2/76) and 21.4% (18/84) of patients during these two parts of the study, respectively, a difference ascribable to the routine determination of tubule function parameters during the second part of the study. CONCLUSION: An exhaustive search for a cause decreases the proportion of male osteoporosis cases that remain idiopathic. In our study, only 28% of cases were classified as idiopathic, a term that probably indicates involvement of multiple interrelated factors.

Ultrasound velocity through the phalanges in normal and osteoporotic patients.

Quantitative ultrasound (US) measurements have been shown to be a new technique assessing bone status. This study aimed to assess a new US instrument, the DBM Sonic 1200(R) (IGEA) which permits the measurement of the speed of sound in the proximal phalanges (SOSp) of the hand. The results obtained were compared with DXA (SOPHOS) and US measurements at the calcaneus (Achilles(R) LUNAR). The in vivo precision expressed by coefficient of variation was 0.91%. Ultrasound measurements of phalanges were significantly correlated with BMD in the entire group of 90 subjects: osteoporotic patients (n = 47) and controls (n = 43) (r = 0.44, femoral neck and 0.45, lumbar spine, P < 0.01). A significant correlation was also found in the control group (r = 0.33, lumbar spine and 0.38, femoral neck, P < 0.05) but not in the osteoporotic group (r = 0.3, lumbar spine and 0.17, femoral neck, P > 0.05). Mean values for 31 postmenopausal, osteoporotic women and age-matched controls showed a significant decrease in US measurements at the phalanges (P < 0.05) and the calcaneus (P < 0.01) as well as bone mineral density (BMD) at the spine and femoral neck (P < 0.01) in the osteoporotic group. A decision threshold for a sensitivity of 80% for osteoporotic fractures resulted in a specificity value of only 37% for SOSp, between 53 to 65% for calcaneus US measurements and 45 to 56% for BMD. The Z score, the odds ratio, the ROC curves, and areas under the curves plotted for the subgroup of 31 fractures and their healthy controls showed poorer values for SOSp than BMD and calcaneus US measurements. In conclusion, US measurements of phalanges seem to be less efficient than calcaneus US and BMD measurements to distinguish osteoporotic from healthy women. Other studies and also prospective studies are required to assess the interest in fracture risk assessment.

Evaluation of bone mineral density in patients with rheumatoid arthritis. Influence of disease activity and glucocorticoid therapy.

OBJECTIVES: To study bone mass and the factors that influence bone mass in rheumatoid arthritis patients versus controls. PATIENTS AND METHODS: 85 patients (73 women) with a mean age of 57 +/- 11 years and a mean disease duration of 13 +/- 9 years were compared to 85 age- and sex-matched controls. Among the patients, 62 (76%) had positive rheumatoid factor tests and 51 (60%) were receiving steroid therapy, with a mean daily dose of 10 +/- 4 mg and a mean duration of 7 +/- 6 years. The following parameters were determined: morning stiffness duration, painful and swollen joint counts, Lee's and Ritchie's indices, Health Assessment Questionnaire score, erythrocyte sedimentation rate, and C-reactive protein. Bone mineral density was measured at the lumbar spine and femoral neck using dual-energy X-ray absorptiometry (Sophos L-XRA). RESULTS: In the nonsteroid-treated patients, bone mineral density was similar to that in controls at the lumbar spine but was decreased by 8% (95% confidence interval [CI], 1.8-14.2%) at the femoral neck (0.76 +/- 0.14 g/cm2 versus 0.83 +/- 0.15 g/cm2; P = 0.03). Decreases of 11.5% (95% CI, 8.1-14.9%) at the lumbar spine and 10.4% (95% CI, 6.4-14.4%) at the femoral neck were found in the steroid-treated patients versus the nonsteroid-treated patients. In the patient group, femoral neck bone mineral density was significantly negatively correlated with age (r = -0.5), the Heath Assessment Questionnaire score (r = -0.27), and the erythrocyte sedimentation rate (r = -0.25), whereas only the first two variables were significantly correlated with lumbar bone mineral density. A multiple linear regression model including age, glucocorticoid use, rheumatoid factor, the Health Assessment Questionnaire score, and the erythrocyte sedimentation rate was constructed and adjusted for the number of variables. This model explained 44.7% of the variance of femoral neck bone mineral density. CONCLUSION: Rheumatoid arthritis is associated with a decrease in bone mass that is most marked in patients with active and/or severe disease and in those who take glucocorticoids.

Contribution of calcaneal ultrasonic assessment to the evaluation of postmenopausal and glucocorticoid-induced osteoporosis.

We evaluated ultrasound propagation through the calcaneus using the Achilles Lunar unit in patients with postmenopausal or glucocorticoid-induced osteoporosis. Speed of sound, broadband ultrasound attenuation and a combination of these two parameters called stiffness were determined. Reproducibility was 0.23%, 2.6%, and 2.6% for these three parameters, respectively. Bone mineral density measured at the spine and femoral neck by absorptiometry was significantly correlated with all three ultrasound parameters in the women with postmenopausal osteoporosis (n = 47) and in the controls (n = 42). In the patients with glucocorticoid-induced osteoporosis (n = 35), only speed of sound was significantly correlated with the bone mineral density measurements. Mean values in the subjects with postmenopausal osteoporosis and in their age-matched controls were 1473 +/- 27.2 m/sec versus 1500.6 +/- 29.6 m/sec for speed of sound, 95.3 +/- 9.6 dB/Mhz versus 105.7 +/- 10.1 dB/Mhz for broadband ultrasound attenuation, and 56.1 +/- 13.2 versus 70.9 +/- 14.1 for stiffness, indicating a significant difference (P < 0.01). Z scores were -0.91, -1.1, -0.93, -0.97, and -1.05 for bone mineral density at the spine, bone mineral density at the femoral neck, speed of sound, broadband ultrasound attenuation and stiffness, respectively. Receiver Operating Characteristic curves showed that there were no statistically significant differences between the ultrasound parameters at the calcaneus and the absorptiometry measurements at the spine and femoral neck. Mean values in glucocorticoid-treated patients and age-matched controls were 1480 +/- 26.9 m/sec versus 1505.1 +/- 30.3 m/sec for speed of sound, 99.2/-11.4 dB/Mhz versus 105.9 +/- -10.2 dB/Mhz for broadband ultrasound attenuation, and 60.7 +/- 14 versus 72.1/14.5 for stiffness, again indicating a significant difference (P < or = 0.01). Z scores were -0.55, -0.65, -0.8, -0.67, and -0.78 for bone mineral density at the spine, bone mineral density at the femoral neck, speed of sound, broadband ultrasound attenuation and stiffness, respectively. Our data suggest that ultrasound parameters measured at the calcaneus are useful for evaluating postmenopausal and glucocorticoid-induced osteoporosis.