Clinical Investigations Response of Cortical Bone to Antiresorptive Treatment L. Hyldstrup 1 J. T. Jørgensen, 2 T. K. Sørensen, 2 L. Baeksgaard 1 1 Department of Endocrinology, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark 2 Clinical Development, Pronosco A/S, Vedbaek, Denmark Received: 9 August 1999 / Accepted: 20 October 2000 / Online publication: 9 March 2001 Abstract. A total of 113 postmenopausal women (69 con- trols, 33 using hormone replacement therapy (HRT), and 11 using bisphosphonate) were evaluated twice over 2 years with a new noninvasive, radiogrammetry-based technique called digital X-ray radiogrammetry (DXR) and conven- tional bone densitometry of the spine, hip, and forearm. Longitudinal changes in bone densitometry were compared with changes captured by DXR: BMD evaluated by DXR (BMD DXR ), cortical thickness of the second metacarpal (CT MC2 ), and porosity of cortical bone. The expected an- nual postmenopausal reduction in BMD in the control group was detected by BMD spine (-0.8%, P < 0.01), BMD hip (-1.6%, P < 0.001), BMD forearm (-1.5%, P < 0.001), DXR-BMD (-0.8%, P < 0.001), and CT MC2 (-1.1%, P < 0.001). In the HRT group, smaller reductions were seen in BMD DXA , but only significant at the hip (-1.0%, P < 0.01) and distal forearm (-1.0%, P < 0.02). In the bisphosphonate group, cortical porosity was significantly reduced (P < 0.025). Comparing longitudinal changes in age-matched subsamples of controls and bisphosphonate treated, BMD DXR , CT MC2 , and porosity of cortical bone all differed significantly (P < 0.01, P < 0.05, P < 0.05, respectively), whereas the BMD DXA measurements did not. In conclusion, DXR provides a densitometry equivalent measurement of the distal forearm and hand and seems to offer new infor- mation on the porosity of cortical bone. This may prove useful in the evaluation of bone loss and offer new insight into the effects of different antiresorptive treatment regi- mens used in the prevention of osteoporosis. Key words: Bisphosphonates — Bone density — Cortical bone — Cortical porosity — Hormonal replacement therapy — Osteoporosis — Radiogrammetry The structure of cortical and trabecular bone and a delicate interplay of the two is believed to influence the biomechan- ical competence of the single bone. This has been demon- strated in vitro [1, 2] and may explain why bone densitom- etry tends to underestimate spontaneous changes in fracture risk as well as treatment effect of certain antiresorptive drugs. Treatment with alendronate reduces the risk of frac- ture, also at the distal forearm [3], but does not influence BMD at the same site [4]. On the other hand, following hormonal replacement therapy (HRT), reduction in forearm fracture risk is paralleled by changes in BMD at the forearm [5, 6]. Several studies have focused on the influence of cortical bone structure on fracture risk [7–10] and attention has been drawn to the differentiated effects of antiresorptive drugs on cortical and trabecular bone [11, 12]. Previous studies have pointed out the potential use of radiogrammetry in detecting effects of HRT on cortical bone [13]. However, it has so far been difficult to evaluate the porosity of cortical bone in vivo. Digital X-ray radiogrammetry (DXR) is based upon the well-known classical radiogrammetry [13–15] and later im- provements [16]. It can provide a BMD estimate together with information on cortical porosity [17]. It is the aim of the present study to evaluate longitudinal changes in cortical bone in treated and untreated postmenopausal women using this technique and conventional bone densitometry by dual energy X-ray absorptiometry (DXA). Materials and Methods The study was designed as an open comparative, nonrandomized observational trial. A group of 126 women who had previously participated in a normative reference study or been categorized as being osteoporotic according to WHO-criteria [18] underwent re- peated examination by DXR (X-posure System™, Pronosco A/S, Vedbaek, Denmark) together with DXA measurements of the spine, hip, and distal forearm. According to treatment status in the period between the two measurements, all subjects were retrospec- tively divided into one of the following three groups: untreated, those who had received HRT, and a group who had been treated with bisphosphonates. Five individuals who had received HRT for less than 90% of the observation period were secondarily ex- cluded. For both patient groups treatment was initiated more than 6 months prior to the initial measurements, in most cases several years earlier. The following measurements were taken with DXA at the ini- tial and follow-up visit: spine BMD (L2-L4), hip BMD (femoral neck), and distal (mid) forearm BMD (10–34 mm proximally of the distal junction of radius and ulna, including both radius and ulna). BMD DXA was measured using a Norland XR-26® densi- tometer (Norland Scientific Instruments, MZ Weesp, The Nether- lands). DXR requires a plain radiograph of the nondominant distal forearm and hand [17]. With a flat-bed scanner (600 × 600 dpi, 12-bit gray-scale), this radiograph is captured as a digital image. Five regions of interest (ROIs) are then automatically identified (Fig. 1). In each region, the cortical thickness and porosity (Fig. 2) Correspondence to: L. Hyldstrup Calcif Tissue Int (2001) 68:135–139 DOI: 10.1007/s002230001204 © 2001 Springer-Verlag New York Inc.