Predicting Subsequent Bone Density Response to Intermittent Cyclical Therapy with Etidronate from Initial Density Response in Patients with Osteoporosis

Abstract

We investigated whether an increase in lumbar spine bone mineral density (LS BMD) at 6 months or at 12 months could predict the response to intermittent cyclical therapy (ICT) with etidronate, defined in one of two ways: (i) an increase in LS BMD at 24 months (improvement) or (ii) an increase in LS BMD > or = 0.028 g/cm2 (significant improvement). The latter is a precision term calculated from test-retest values for LS BMD in osteoporotic patients. Two hundred and forty-seven patients (32 men; 5 premenopausal and 210 postmenopausal women) were followed for 24 months by dual-energy X-ray absorptiometry (DXA) and were not taking estrogen, calcitonin or fluoride during treatment with ICT-etidronate. One hundred and fifty patients had a LS BMD measurement after 6 months of treatment with ICT-etidronate and 205 patients had one at 12 months. Baseline characteristics (mean;SD) were as follows: age, 66;11 years; years since menopause, 21;10; number of vertebral fractures at baseline, 0.87;1.26; LS BMD T-score, -2.8; 1.2. After 24 months of treatment with ICT-etidronate, 81% of the patients had an improvement, and 55% had a significant improvement at the LS. Only 6% significantly lost bone (loss of 0.028 g/cm2 or more). The mean percent change from baseline in LS BMD was 5.1% (95% confidence interval 4.2% to 6.0%). The results for men and postmenopausal women were similar to those for the entire group. Accuracy and sensitivity were marginally, but not significantly, higher when response was predicted using 12 month versus 6 month LS BMD measurements. The positive predictive values of improvement at 6 or 12 months were 89% and 90% respectively for improvement at 24 months, and 66% and 68% for significant improvement at 24 months. Identification of nonresponders was less successful and similar at 6 months and 12 months. Forty percent and 39% of the patients, who had no improvement at 6 or 12 months respectively, also had no improvement at 24 months, i.e., were true negatives, while 77% and 71% had no significant improvement at 24 months. The results may reflect slow response in a small subgroup of patients rather than nonresponse; however, no response at 1 year might identify patients whose rate of response is sufficiently slow that alternative therapy is justified. These data demonstrate a good response rate to ICT-etidronate and may help reduce the need for follow-up BMD measurements in those who show an early improvement.

Synchrotron Radiation Microtomography Allows the Analysis of Three-Dimensional Microarchitecture and Degree of Mineralization of Human Iliac Crest Biopsy Specimens: Effects of Etidronate Treatment

“…Indeed, although a significant increase in BMD of trabecular sites was observed in the alendronate‐treated patients, (4) it was shown that no increase in bone mass (i.e., bone volume to total volume [BV/TV] from quantitative histomorphometry on iliac crest bone biopsy specimens) occurred in patients after a 3‐year treatment with alendronate as compared with the placebo group. Significant increases in BMD also were observed in patients under other BPs, (1,5–7) including etidronate (8,2) . These data suggested that parameters other than true bone mass might explain changes in BMD or reduced fracture incidence under treatment.…”

Farnesyl Diphosphate Synthase (Fdrs) and Geranylgeranyl Diphosphate Synthase (Ggsp1) Gene Polymorphisms and Efficiency of Therapy With Bisphosphonates in Russian Women With Postmenopausal Osteoporosis: A Pilot Study

“…Существование резистентных к БФ пациентов пред-ставляет потенциальную проблему для клиницистов [4]. Идентифицировать больных с отсутствием ответа или со слабым ответом на БФ можно по характеру динамики уровня биохимических маркеров костного метаболизма через 3 мес от начала лечения [5] или изменения МПК че-рез 6-12 мес [6].…”

“…Известно, что увеличение МПК на фоне лечения БФ происходит медленно, однако в одном из исследований было показано, что любое улучшение МПК через 6 мес яв-ляется предиктором последующего положительного эффе-кта БФ [6]. В нашей пилотной работе для идентификации ответивших и не ответивших на лечение БФ мы выбрали 12-месячный период вмешательства.…”

Genetic Polymorphism of Geranylgeranyl Diphosphate Synthase (GGSP1) Predicts Bone Density Response to Bisphosphonate Therapy in Korean Women

“…However, a well designed study to predict subsequent BMD response to bisphosphonate from early BMD response suggested that any improvement in BMD at 6 or 12 months is strongly indicative of subsequent BMD response 18. Therefore, we assumed that one year follow-up BMD would be sufficient to classify "non-responder(s)" and "responders".…”

“…Although bisphosphonate is known as a potent inhibitor of bone resorption and used for the treatment and prevention of osteoporosis, non-responders to bisphosphonate therapy is of potential concern to clinicians and patients 16. Several studies have been conducted to identify high risk groups of non-responder(s), based on baseline characteristics,14 early changes in biochemical markers of bone turnover17 and early changes in BMD 18. However, little is known about the common characteristics of non-responder(s) to help clinicians decide whether to initiate bisphosphonates or not.…”