C. Pondrelli

Prevention of corticosteroid-induced osteoporosis with alendronate in sarcoid patients.

Abstract. Prolonged corticosteroid administration, as often required in the treatment of sarcoidosis, increases the risk of osteoporosis and fracture. The aim of the present study was to evaluate the usefulness of alendronate, a third generation bisphosphonate, in preventing corticosteroid-induced osteoporosis. Forty-three consecutive, previously untreated, sarcoid patients (17 men and 26 premenopausal women) were included in the study: 13 needed no treatment and served as controls (Group 1) and 30 needed glucocorticoids (prednisone) and were randomly selected to also receive either placebo (n = 15, Group 2) or alendronate 5 mg/day (n = 15, Group 3). Bone mineral density (BMD) at the ultradistal radius by dual photon absorptiometry (Osteograph 1000, NIM, Verona, Italy) and biochemical markers of bone turnover were measured at baseline and after 6 and 12 months of glucocorticoid therapy. No significant difference was found between Groups 2 and 3 in the mean cumulative dose of prednisone (4945 ± 1956 mg and 5110 ± 2013 mg, respectively). At the end of the study period, BMD increased by 0.8% in the alendronate-treated group; in the placebo-treated group, BMD decreased by 4.5%. The difference between groups was significant (P < 0.01, ANOVA). A significant decrease in markers of bone formation was found in all patients treated with prednisone (Groups 2 and 3), independently of alendronate. Alendronate, however, counteracted the increase in markers of bone resorption induced by glucocorticoid therapy. Our data suggest that alendronate is effective in preventing glucocorticoid-induced bone loss in sarcoid patients. Further studies on alendronate use in steroid-induced osteoporosis are needed.

Ultrasound parameters in osteoporotic patients treated with salmon calcitonin: A longitudinal study

Speed of sound (SOS) and broadband ultrasound attenuation (BUA) of ultrasound (US) in bone have been proposed as alternatives to radiation-based methods for the quantitative assessment of osteoporosis. However, the usefulness of US in monitoring response to treatment in osteoporotic patients has yet to be defined. To compare US with bone mineral density (BMD), we studied 112 osteoporotic women (age range 50–64 years). Seventy-eight of them were treated with salmon calcitonin nasal spray (CT; 200 IU/day, 1 month on and 1 month off) and calcium (500 mg/day); 34 patients were given only calcium. One hundred and four women complied with treatment throughout the 2-year study period. At baseline and after 1 and 2 years we measured BMD at lumbar spine by dual-energy X-ray absorptiometry (DXA), and SOS, BUA and Stiffness index, by an Achilles ultrasound unit. Moreover, biochemical markers of bone turnover (alkaline phosphatase, osteocalcin and hydroxyproline) were also measured at baseline and after 6, 12 and 24 months. In the calcitonin-treated group at the end of the study period BMD had increased by 1.99%, SOS by 0.20%, BUA by 0.88% and Stiffness by 2.12%. By contrast in the calcium-treated group all parameters had decreased (BMD, −2.66%; SOS, −0.55%; BUA, −3.30%; Stiffness, −6.0%) by the end of the study period. The differences between groups were significant for BMD, SOS and Stiffness. At baseline a significant, but weak correlation was found between BMD and US parameters. The correlation coefficients between percentage changes at the end of the study period, in BMD and in SOS, BUA and Stiffness, were all significant (p<0.001), being 0.41, 0.53 and 0.57 respectively. In conclusion, ultrasound measurements carried out in conjunction with BMD measurements will yield a more comprehensive assessment of skeletal status and may be helpful in monitoring the response to treatment in osteoporotic patients.

The Usefulness of Bone Turnover in Predicting the Response to Transdermal Estrogen Therapy in Postmenopausal Osteoporosis

Transdermal estrogen therapy is now an accepted form of treatment for postmenopausal osteoporosis. Ninety postmenopausal osteoporotic women were randomized to receive either transdermal estrogen (0.05 mg/day 17β‐estradiol) and calcium (n = 45) or calcium alone (n = 45). The study period was 2 years. Bone mineral density (BMD) at the lumbar spine (by dual‐energy X‐ray absorptiometry [DXA]) and markers of bone turnover (alkaline phosphatase, osteocalcin, hydroxyproline, pyridinoline cross‐links) were assessed at baseline and after 1 and 2 years. In the estrogen‐treated group, BMD showed a significant increase (p < 0.001) both after 1 and 2 years, with a reduction in biochemical markers. To investigate the effectiveness of estrogen treatment of postmenopausal osteoporosis in relation to bone turnover, we also divided the patients on the basis of bone turnover, as assessed by measurement of whole body retention (WBR) of99mTc‐methylene diphosphonate. WBR revealed that 26 patients had high bone turnover (HT) and 55 had low bone turnover (LT). The response to estrogen was greater in the HT patients than in the LT patients; in fact BMD increased by 5.7 and 6.6% in HT patients and by 2.6 and 2.7% in LT patients after 1 and 2 years, respectively. In conclusion, the present study demonstrates that, while the BMD decreases in the patients treated with calcium alone, 2‐year treatment with transdermal estrogen increases axial BMD and that the response to estrogen treatment is influenced by bone turnover. Therefore, the evaluation of bone turnover may be useful to identify those postmenopausal osteoporotic women who may especially benefit from treatment with estrogen.

Osteogenesis Imperfecta: Bone Turnover, Bone Density, and Ultrasound Parameters

Abstract. We studied 21 patients (11 men and 10 women) with osteogenesis imperfecta (OI) and 21 age- and sex-matched controls. In all patients we measured serum levels of total alkaline phosphatase (ALP), type I procollagen carboxy-terminal propeptide (PICP), osteocalcin (BGP), urinary excretion of hydroxyproline (HOP/Cr), and pyridinoline crosslinks (Pyr/Cr). Bone mineral density was measured at the distal radius (BMD-R) and at the lumbar spine (BMD-LS) by dual X-ray absorptiometry (DXA). Ultrasound parameters were also performed at the calcaneous with the Achilles device and at the phalanxes with DBM Sonic 1200. A significant reduction (P < 0.001) in BMD and in ultrasound parameters was found in OI patients compared with normals. PICP was significantly reduced in the OI patients compared with controls (P < 0.001); other markers of bone turnover were higher in OI than in controls, but the difference did not reach the statistical significance. A significant correlation (P < 0.05) was found between PICP and BMD at the lumbar spine and between PICP and ultrasound parameters at the calcaneous. On the basis of our data, we conclude that patients with OI show low values of BMD and ultrasound parameters; therefore in these patients, not only is bone mass disturbed but also bone quality. The reduced levels of PICP in OI patients confirm that most OI patients have defects in collagen I biosynthesis. These defects may contribute to the fragility of OI bone by interfering with complete mineralization and/or normal tissue structure. PICP may be considered a useful marker in the clinical management of OI.

Bone Turnover and the Response to Alendronate Treatment in Postmenopausal Osteoporosis

Abstract. This study investigated whether bone turnover influences the response to alendronate in women with postmenopausal osteoporosis. One hundred postmenopausal osteoporotic women were randomized to receive either alendronate (10 mg/day) plus calcium (1000 mg/day) (n = 50) or calcium alone (n = 50). Vertebral and radial bone density, measured by DXA, and markers of bone turnover were assessed at baseline and after 1 and 2 years. At the end of treatment, alendronate users showed an increase of 5.0% and 2.3%, respectively, at the lumbar spine and ultradistal radius; in the group treated only with calcium, bone mineral density (BMD) decreased by 1.6% at the lumbar spine and 1.3% at the ultradistal radius. The difference between the two groups was significant (P < 0.001). The patients were divided into high (HT) or low (LT) bone turnover groups, as assessed by 24-hour whole body retention (WBR%) of 99mTc-methylene-diphosphonate. The response to alendronate treatment was greater in HT patients compared with LT patients. In fact, at the end of the study period, BMD at the lumbar spine had increased by 7.9% in HT patients and by 3.0% in LT patients; the difference between the two groups was significant (P < 0.001). No significant difference between the two groups was found for BMD at the ultradistal radius. In conclusion, the present study demonstrates that 2-year treatment with alendronate has highly positive effects on bone mass at both the lumbar spine and ultradistal radius. The increase in bone mass, especially at the axial level, is influenced by bone turnover. Therefore, the evaluation of bone turnover may be useful in predicting the response to alendronate treatment.

Ultrasonographic assessment of bone in normal Italian males and females

Recently ultrasound techniques have been proposed to evaluate skeletal status. Speed of sound and attenuation through the bone are the ultrasound properties currently used to assess bone strength and fragility. The speed of sound in m s-1 (SOS), broadband ultrasound attenuation in dB MHz-1 (BUA) and stiffness (S) in 134 healthy females (age range 10-90 years) and in 100 healthy males (age range 10-93 years) was measured using the Achilles scanner (Lunar Corp., Madison, WI, USA). A polynomial function was applied to the observed data to evaluate a pattern of age-related BUA, SOS and S changes. Peak values of SOS, BUA and S were reached in both sexes at the age of 30 years. Average decreases of 12.9% in BUA, 4.9% in SOS and 28.9% in S were found in men aged between 30 and 90 years. In women average decreases of 17.2% in BUA, 4.2% in SOS and 31.9% in S were discovered in those aged between 30 and 90 years. The analysis of SOS, BUA and S changes between pre- and post-menopausal women revealed a significant decrease of these parameters with years since menopause. These data indicate an age-related decrease of ultrasound signals in both sexes. Furthermore, this technique is able to detect, in females, menopause related changes due to oestrogen failure. In contrast, in males, the age-related loss of ultrasound signals appears to be more linear.

Usefulness of ultrasound in Sudeck's atrophy of the foot.

Abstract. Quantitative ultrasound (QUS) of bone has been proposed as an inexpensive and radiation-free device method of assessing skeletal status. QUS has been widely used in the assessment of osteoporosis. Until now only few data are available on the usefulness of QUS in different disorders, such as Sudecks atrophy. To evaluate the ability of QUS in the diagnosis and monitoring of regional osteoporosis, we investigated 19 patients (12 women and 7 men, age range 30–65 years) with osteoporosis of the foot (Sudecks atrophy), as evidenced by X-ray study and Technetium-99 bone scan. In all patients we measured speed of sound (SOS), broadband ultrasound attenuation (BUA), and stiffness of the calcaneus using Lunar Achilles Ultrasound, both in the affected and unaffected foot. Bone mineral density at the lumbar spine, by DXA (Hologic QDR 1000), was also performed. QUS was repeated after 3 and 6 months of treatment with salmon calcitonin (100 IU I.M. every second day). At baseline, SOS, BUA, and stiffness, expressed as T-score, were −1.9, −2.4, and −2.4 in unaffected feet and −2.9, −5.1, and −4.3, respectively, in affected feet. The difference between the unaffected and affected foot was significant for SOS, BUA, and stiffness (P < 0.001). No significant difference was found in QUS parameters in the unaffected foot during the study period. After 3 and 6 months of treatment, SOS increased in the affected foot by 0.2% and 0.3%, BUA increased by 6.2% and 8.2%, and stiffness by 7.5% and 11.1%, respectively. In conclusion, BUA and stiffness seem to be influenced more than SOS by Sudecks atrophy; QUS, namely, BUA and stiffness, significantly increase with calcitonin treatment. In conclusion, QUS is a sensitive tool in the diagnosis of Sudecks atrophy of the foot and is adequate for measuring improvement in bone status following treatment.