Original Article Heel Ultrasonography in Monitoring Alendronate Therapy: A Four- Year Longitudinal Study S. Gonnelli, C. Cepollaro, A. Montagnani, S. Martini, L. Gennari. M. Mangeri and C. Gennari Institute of Internal Medicine, University of Siena, Siena, Italy Abstract. The possibility of using quantitative ultra- sound (QUS) in monitoring the response to antiresorp- tive drugs has yet to be defined. The aim of the present study was to evaluate whether heel ultrasonography, considering its characteristics of long-term precision, is able to monitor osteoporotic patients treated with alendronate. We studied 150 postmenopausal osteoporo- tic women (age 59.6 + 5.3 years) treated with alendronate and calcium (n = 74) or with calcium alone (n = 76) for 4 years. At baseline and after 12, 24, 36 and 48 months, we measured bone mineral density (BMD) at the lumbar spine by dual-energy X-ray absorptiometry (DXA, Hologic 4500), and speed of sound (SOS), broadband ultrasound attenuation (BUA) and Stiffness at the calcaneus by Achilles plus. More- over, the longitudinal precision of QUS parameters was assessed by measuring 10 subjects once a month for 1 year and, on the basis of the coefficients of variation we obtained, we calculated the Least Significant Change between two measurements. In the alendronate-treated patients, at year 1, BMD increased by 4.2%, SOS by 0.4%, BUA by 1.1% and Stiffness by 3.2%; at year 2, BMD increased by 5.0%, SOS by 0.7%, BUA by 1.4% and Stiffness by 5.7%. At year 3, BMD increased by 6.2%, SOS by 0.9%, BUA by 1.8% and Stiffness by 7.6%. At the end of the study period, BMD increased by 7.6%, SOS by 1.2%, BUA by 1.9% and Stiffness by 9.0%. The minimal significant difference between two measurements was 0.8% for SOS, 5.6% for BUA and 5.0% for Stiffness. Among the QUS parameters, Stiffness showed the greatest total treatment effect and a longitudinal sensitivity which was only slightly lower than BMD. The MTI, which represents the period between scans required to show that a ‘true’ change has occurred, was 1.8, 2.7, 11.9 and 2.2 years for BMD, SOS, BUA and Stiffness respectively. Therefore, although the spinal BMD remains the optimal method, QUS at the heel, and in particular Stiffness, seems to be a sensitive tool for monitoring the response to alendronate. Keywords: Alendronate; Longitudinal sensitivity; Quantitative ultrasound Introduction The awareness of osteoporosis as an important health problem and the development of treatments with proven efficacy are increasing the demand for diagnostic tools in the management of patients with osteoporosis [1]. Dual- energy X-ray absorptiometry (DXA) is the current gold standard in the clinical assessment of osteoporosis [2], even though the diagnosis of osteoporosis should also include a clinical evaluation [3]. However, DXA devices are relatively expensive and require patients to be referred to hospital-based facilities. In recent years there has been growing scientific and clinical interest in quantitative ultrasound (QUS) as an alternative method to X-ray absorptiometry for assessing skeletal status [4]. In vitro experiences have suggested that QUS may give information about not only bone density but also architecture and elasticity [5,6], even though recent reports have demonstrated that ultrasound parameters are mostly related to bone mineral density (BMD) [7,8]. This fact, coupled with several advantages including the Osteoporos Int (2002) 13:415–421 ß 2002 International Osteoporosis Foundation and National Osteoporosis Foundation Osteoporosis International Correspondence and offprint requests to: S. Gonnelli, MD, Institute of Internal Medicine, University of Siena, Policlinico Le Scotte, Viale Bracci, I-53100 Siena, Italy. Tel: +39 0577 585468. Fax: +39 0577 270281. e-mail: gonnelli@unisi.it