Denosumab effects on bone density and turnover in postmenopausal women with low bone mass with or without previous treatment

Tsourdi, Elena; Makras, Polyzois; Rachner, Tilman D.; Polyzos, Stergios; Rauner, Martina; Mandanas, Stylianos; Hofbauer, Lorenz C.; Anastasilakis, Athanasios D.

Affiliations

¹Department of Medicine III, Technische Universität Dresden Medical Center, Dresden, Germany

²Center for Healthy Aging, Technische Universität Dresden Medical Center, Dresden, Germany

³Department of Endocrinology and Diabetes, 251 Hellenic Force & VA General Hospital, Athens, Greece

⁴First Department of Pharmacology, Medical School, Aristotle University of Thessaloniki, Greece

⁵Department of Endocrinology, 424 General Military Hospital, 54638 Thessaloniki, Greece

⁶Center for Regenerative Therapies Dresden, Technische Universität Dresden, Germany

Abstract and keywords

Purpose: Prior osteoporosis therapies may affect the skeletal response to denosumab. We compared the effect of denosumab (60 mg every 6 months for 12 months) on bone mineral density and bone metabolism parameters in postmenopausal women with low bone mass who were either treatment-naïve (n = 30), or previously treated either with zoledronic acid (n = 30), or teriparatide (n = 22).

Methods: We assessed lumbar spine bone mineral density (BMD) and measured serum concentrations of the bone turnover markers pro-collagen type 1 N-terminal propeptide (PINP) and C-terminal-cross-linking telopeptide of type 1 collagen (CTX), as well as sclerostin, dickkopf-1 (Dkk-1), and myostatin.

Results: Lumbar spine BMD increased equivalently in all three groups after 12 months of denosumab compared to baseline (p < 0.001). Serum PINP and CTX decreased significantly with denosumab in pre-treated women reaching the same nadir levels as in treatment-naïve patients (p < 0.001). Women pre-treated with teriparatide displayed lower baseline myostatin concentrations as compared to the other two groups (p < 0.001). Changes in lumbar spine BMD in teriparatide pre-treated women correlated with changes in bone turnover markers and myostatin.

Conclusions: Denosumab induced similar increases in lumbar spine BMD in treatment-naïve and pre-treated patients and suppressed serum PINP and CTX to the same levels regardless of prior treatments. In teriparatide pre-treated patients the magnitude of change in bone turnover markers is associated with BMD response.

Keywords: Denosumab; Zoledronic acid; Teriparatide; Bone remodeling; Wnt-inhibitors; Myostatin

Links

DOI: 10.1016/j.bone.2018.10.001

PubMed: 30292818

WoS: 000458471700006

History

Received: 2018-06-5

Revised: 2018-09-29

Accepted: 2018-10-3

Online: 2018-10-4

Cited Works (9)

Year	Entry
2009	Brown JP, Prince RL, Deal C, Recker RR, Kiel DP, Gregorio LHd, Hadji P, Hofbauer LC, Álvaro-Gracia JM, Wang H, Austin M, Wagman RB, Newmark R, Libanati C, San Martin J, Bone HG. Comparison of the effect of denosumab and alendronate on BMD and biochemical markers of bone turnover in postmenopausal women with low bone mass: a randomized, blinded, phase 3 trial. J Bone Miner Res. January 2009;24(1):153-161.
2015	Leder BZ, Tsai JN, Uihlein AV, Wallace PM, Lee H, Neer RM, Burnett-Bowie S-AM. Denosumab and teriparatide transitions in postmenopausal osteoporosis (the DATA-Switch study): extension of a randomised controlled trial. Lancet. September 19-25, 2015;386(9999):1147.
2007	Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, Cosman F, Lakatos P, Leung PC, Man Z, Mautalen C, Mesenbrink P, Hu H, Caminis J, Tong K, Rosario-Jansen T, Krasnow J, Hue TF, Sellmeyer D, Eriksen EF, Cummings SR; HORIZON Pivotal Fracture Trial. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. NEJM. May 3, 2007;356(18):1809-1822.
2017	Bone HG, Wagman RB, Brandi ML, Brown JP, Chapurlat R, Cummings SR, Czerwiński E, Fahrleitner-Pammer A, Kendler DL, Lippuner K, Reginster J-Y, Roux C, Malouf J, Bradley MN, Daizadeh NS, Wang A, Dakin P, Pannacciulli N, Dempster DW, Papapoulos S. 10 years of denosumab treatment in postmenopausal women with osteoporosis: results from the phase 3 randomised FREEDOM trial and open-label extension. Lancet Diabetes Endocrinol. July 2017;5(7):513-523.
2010	Kendler DL, Roux C, Benhamou CL, Brown JP, Lillestol M, Siddhanti S, Man H-S, San Martin J, Bone HG. Effects of denosumab on bone mineral density and bone turnover in postmenopausal women transitioning from alendronate therapy. J Bone Miner Res. January 2010;25(1):72-81.
2011	Bone HG, Bolognese MA, Yuen CK, Kendler DL, Miller PD, Yang Y-C, Grazette L, San Martin J, Gallagher JC. Effects of denosumab treatment and discontinuation on bone mineral density and bone turnover markers in postmenopausal women with low bone mass. J Clin Endocrinol Metab. April 2011;96(4):972-980.
2018	Cummings SR, Ferrari S, Eastell R, Gilchrist N, Jensen J-EB, McClung M, Roux C, Törring O, Valter I, Wang AT, Brown JP. Vertebral fractures after discontinuation of denosumab: a post hoc analysis of the randomized placebo-controlled FREEDOM trial and its extension. J Bone Miner Res. February 2018;33(2):190-198.
2001	Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster J-Y, Hodsman AB, Eriksen EF, Ish-Shalom S, Genant HK, Wang O, Mellström D, Oefjord ES, Marcinowska-Suchowierska E, Salmi J, Mulder H, Halse J, Sawicki AZ, Mitlak BH. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. NEJM. May 10, 2001;344(19):1434-1441.
2009	Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR, Delmas P, Zoog HB, Austin M, Wang A, Kutilek S, Adami S, Zanchetta J, Libanati C, Siddhanti S, Christiansen C; FREEDOM Trial. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. NEJM. August 20, 2009;361(8):756-765.

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Year	Entry
2020	Jones AR, Sim I-W. Denosumab failure associated with escape from suppression of bone resorption. Bone. February 2020;131:115157.
2020	LaCombe JM, Roper RJ. Skeletal dynamics of Down syndrome: a developing perspective. Bone. April 2020;133:115215.
2022	Wadiura LI, Butylina M, Reinprecht A, Aretin M-B, Mischkulnig M, Gleiss A, Pietschmann P, Kerschan-Schindl K. Denosumab for prevention of acute onset immobilization-induced alterations of bone turnover: a randomized controlled trial. J Bone Miner Res. November 2022;37(11):2156-2164.