Effect of Strontium Ranelate on Lumbar Spine Bone Mineral Density in Women with Established Osteoporosis Previously Treated with Teriparatide

Abstract

Teriparatide (TPTD – recombinant human parathyroid hormone 1–34) markedly increases bone mineral density (BMD) and reduces fracture risk. Sequential treatment with an antiresorptive agent is believed to preserve or further increase BMD. Strontium ranelate (SR) is thought to uncouple bone remodeling resulting in increased BMD and reduced fracture risk. We aimed to evaluate the effect of SR on BMD in women with established osteoporosis previously treated with TPTD. Nineteen out of the consecutive 23 initially recruited postmenopausal Caucasian women (aged 65.9±1.8 years) with established osteoporosis completed treatment with TPTD, 20 μg daily for 18 months, followed by SR 2 g daily for 12 months. Lumbar spine BMD was measured by dual-energy X-ray absorptiometry (DXA) pre- and post-TPTD administration, as well as twelve months post-SR administration. Blood samples for bone-specific alkaline phosphatase (BSAP) and C-terminal telopeptide of type 1 collagen (CTx) were obtained at the same time points. Lumbar spine BMD increased significantly after 18 months of TPTD (p<0.001) and further improved with sequential SR treatment (p=0.033). Serum BSAP and CTx increased significantly with TPTD (p=0.008 and 0.017, respectively) and reduced to baseline levels after SR treatment (p=0.031 and 0.019, respectively). The change in BSAP was positively correlated with the change in CTx during both TPTD (r=0.641, p=0.007) and SR treatment (r=0.539, p=0.026). In conclusion, our data suggest that SR following TPTD administration further increases BMD and could represent an effective sequential treatment.

parathyroid hormone - osteoanabolic - sequential treatment - bone markers - postmenopausal osteoporosis

References

• 1 Johnell O, Kanis JA, Oden A, Johansson H, Laet C De, Delmas P, Eisman JA, Fujiwara S, Kroger H, Mellstrom D, Meunier PJ, Melton 3rd LJ, O’Neill T, Pols H, Reeve J, Silman A, Tenenhouse A. Predictive value of BMD for hip and other fractures.  J Bone Miner Res. 2005;  20 1185-1194
• 2 Leslie WD, Tsang JF, Caetano PA, Lix LM. Effectiveness of bone density measurement for predicting osteoporotic fractures in clinical practice.  J Clin Endocrinol Metab. 2007;  92 77-81
• 3 Melton 3rd LJ, Chrischilles EA, Cooper C, Lane AW, Riggs BL. Perspective. How many women have osteoporosis?.  Bone Miner Res. 1992;  7 1005-1010
• 4 Lenchik L, Kiebzak GM, Blunt BA. What is the role of serial bone mineral density measurements in patient management?.  J Clin Densitom. 2002;  5 ((Suppl)) S29-S38
• 5 Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster JY, Hodsman AB, Eriksen EF, Ish-Shalom S, Genant HK, Wang O, Mitlak BH. Effect of parathyroid hormone (1–34) on fractures and bone mineral density in postmenopausal women with osteoporosis.  N Engl J Med. 2001;  344 1434-1441
• 6 Body JJ, Gaich GA, Scheele WH, Kulkarni PM, Miller PD, Peretz A, Dore RK, Correa-Rotter R, Papaioannou A, Cumming DC, Hodsman AB. A randomized double-blind trial to compare the efficacy of teriparatide [recombinant human parathyroid hormone (1–34)] with alendronate in postmenopausal women with osteoporosis.  J Clin Endocrinol Metab. 2002;  87 4528-4535
• 7 Meunier PJ, Roux C, Seeman E, Ortolani S, Badurski JE, Spector TD, Cannata J, Balogh A, Lemmel EM, Pors-Nielsen S, Rizzoli R, Genant HK, Reginster JY. The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis.  N Engl J Med. 2004;  350 459-468
• 8 Reginster JY, Seeman E, Vernejoul MC De, Adami S, Compston J, Phenekos C, Devogelaer JP, Curiel MD, Sawicki A, Goemaere S, Sorensen OH, Felsenberg D, Meunier PJ. Strontium ranelate reduces the risk of nonvertebral fractures in postmenopausal women with osteoporosis: Treatment of Peripheral Osteoporosis (TROPOS) study.  J Clin Endocrinol Metab. 2005;  90 2816-2822
• 9 Blake GM, Fogelman I. The correction of BMD measurements for bone strontium content.  J Clin Densitom. 2007;  10 259-265
• 10 Ammann P, Badoud I, Barraud S, Dayer R, Rizzoli R. Strontium ranelate treatment improves trabecular and cortical intrinsic bone tissue quality, a determinant of bone strength.  J Bone Miner Res. 2007;  22 1419-1425
• 11 Rittmaster RS, Bolognese M, Ettinger MP, Hanley DA, Hodsman AB, Kendler DL, Rosen CJ. Enhancement of bone mass in osteoporotic women with parathyroid hormone followed by alendronate.  J Clin Endocrinol Metab. 2000;  85 2129-2134
• 12 Marie PJ. Strontium ranelate: a physiological approach for optimizing bone formation and resorption.  Bone. 2006;  38 ((Suppl 1)) S10-S14
• 13 Anastasilakis AD, Goulis DG, Polyzos SA, Gerou S, Koukoulis G, Kita M, Avramidis A. Serum osteoprotegerin and RANKL are not specifically altered in women with postmenopausal osteoporosis treated with teriparatide or risedronate: a randomized controlled trial.  Horm Metab Res. 2008;  40 281-285
• 14 Anastasilakis AD, Polyzos SA, Goulis DG, Slavakis A, Efstathiadou Z, Kita M, Koukoulis G, Avramidis A. Endogenous intact PTH is suppressed during teriparatide (rhPTH 1–34) administration in postmenopausal women with established osteoporosis.  Endocr J. 2008;  55 613-616
• 15 Delmas PD. Markers of bone turnover for monitoring treatment of osteoporosis with antiresorptive drugs.  Osteoporos Int. 2000;  11 ((Suppl 6)) S66-S76
• 16 Black DM, Bilezikian JP, Ensrud KE, Greenspan SL, Palermo L, Hue T, Lang TF, MacGowan JA, Rosen CJ. One year of alendronate after one year of parathyroid hormone (1–84) for osteoporosis.  N Engl J Med. 2005;  353 555-565
• 17 Anastasilakis AD, Goulis DG, Polyzos SA, Gerou S, Ballaouri I, Efstathiadou Z, Kita M, Avramidis A. No difference between strontium ranelate and calcium/vitamin D on bone turnover markers in women with established osteoporosis previously treated with teriparatide: a randomized controlled trial.  Clin Endocrinol (Oxf). 2009;  , epub ahead of print
• 18 Lindsay R, Scheele WH, Neer R, Pohl G, Adami S, Mautalen C, Reginster JY, Stepan JJ, Myers SL, Mitlak BH. Sustained vertebral fracture risk reduction after withdrawal of teriparatide in postmenopausal women with osteoporosis.  Arch Intern Med. 2004;  164 2024-2030
• 19 Eastell R, Hadji P, Farrerons J, Audran M, Boonen S, Brixen K, Melo Gomes J, Obermayer-Pietsch B, Avramidis A, Sigurdsson G, Glueer C, Cleall S, Marin F, Nickelsen T. Comparison of 3 sequential treatment regimens of teriparatide: final results from the EUROFORS Study.  J Bone Miner Res. 2006;  21 ((Suppl 1)) S70
• 20 Chen P, Miller PD, Delmas PD, Misurski DA, Krege JH. Change in lumbar spine BMD and vertebral fracture risk reduction in teriparatide-treated postmenopausal women with osteoporosis.  J Bone Miner Res. 2006;  21 1785-1790
• 21 Delmas P, Seeman E. Changes in bone mineral density explain little of the reduction in vertebral or nonvertebral fracture risk with anti-resorptive therapy.  Bone. 2004;  34 599-604

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