Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Mar;3(1):45-52.
doi: 10.1016/j.afos.2016.12.001. Epub 2017 Jan 17.

Bone turnover rate and bone formation/resorption balance during the early stage after switching from a bone resorption inhibitor to denosumab are predictive factors of bone mineral density change

Affiliations

Bone turnover rate and bone formation/resorption balance during the early stage after switching from a bone resorption inhibitor to denosumab are predictive factors of bone mineral density change

Shinichi Nakatoh. Osteoporos Sarcopenia. 2017 Mar.

Abstract

Objectives: This study aimed to investigate the correlation between bone mineral density (BMD) and the turnover rate [√(MoMf2 + MoMr2), multiple of median formation (MoMf) was calculated as bone-specific alkaline phosphatase (BAP) value/18.6 and multiple of median resorption (MoMr) as tartrate-resistant acid phosphatase 5b (TRACP-5b) value/463] and the balance (MoMf/MoMr) and to compare differences in therapeutic effects evoked by differences in previous treatments.

Methods: In 51 osteoporotic women treated with bisphosphonates (BPs) or selective estrogen receptor modulators (SERMs), BMD was measured at 0, 24, and 48 weeks after denosumab administration. The values of BAP and TRACP-5b were measured at 0, 4, 12, 24, 36, and 48 weeks.

Results: The turnover rate decreased at week 4 and decreased further at week 12. The balance indicated a relative predominantly formative state at week 4. This balance became higher in the SERM group than in the BP group at week 4. A correlation was observed between the rate of BMD change and turnover rate at weeks 0 and 4.

Conclusions: It is necessary to evaluate the turnover rate and balance to determine the therapeutic effect of denosumab, which induces dissociation between the trends in the bone turnover markers. Turnover rate and balance during the early stages of denosumab treatment may be predictive factors of BMD. When switching from bone resorption inhibitors to denosumab, it was necessary to consider the beginning values that were affected by the previous treatment. The state of relative anabolism is greater at 4 weeks when the previous treatment involved SERMs rather than BPs.

Keywords: Bone mineral density; Bone-specific alkaline phosphatase; Denosumab; Osteoporosis; Tartrate-resistant acid phosphatase 5b.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Scatter diagram for multiple of median (MoM) formation and MoM resorption in the bisphosphonate group (●) and selective estrogen receptor modulator group (▲) at weeks 0 (a), 4 (b), 12 (c), and 24 (d).
Fig. 2
Fig. 2
Periodic changes in turnover rate (a), balance (b), bone alkaline phosphatase (BAP) (c), tartrate-resistant acid phosphatase 5b (TRACP-5b) (d), lumbar spine (e) and femur (f) bone mineral density (BMD) in the bisphosphonate (BP) and selective estrogen receptor modulator (SERM) groups.

References

    1. McClung M.R., Lewiecki E.M., Cohen S.B., Bolognese M.A., Woodson G.C., Moffett A.H. Denosumab in postmenopausal women with low bone mineral density. N Engl J Med. 2006;354:821–831. - PubMed
    1. Cummings S.R., Martin J.S., McClung M.R., Siris E.S., Eastell R., Reid I.R. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009;361:756–765. - PubMed
    1. McClung M.R., Lewiecki E.M., Geller M.L., Bolognese M.A., Peacock M., Weinstein R.L. Effect of denosumab on bone mineral density and biochemical markers of bone turnover: 8-year results of a phase 2 clinical trial. Osteoporos Int. 2013;24:227–235. - PMC - PubMed
    1. Sugimoto T., Matsumoto T., Hosoi T., Miki T., Gorai I., Yoshikawa H. Three-year denosumab treatment in postmenopausal Japanese women and men with osteoporosis: results from a 1-year open-label extension of the Denosumab Fracture Intervention Randomized Placebo Controlled Trial (DIRECT) Osteoporos Int. 2015;26:765–774. - PubMed
    1. Papapoulos S., Lippuner K., Roux C., Lin C.J., Kendler D.L., Lewiecki E.M. The effect of 8 or 5 years of denosumab treatment in postmenopausal women with osteoporosis: results from the FREEDOM Extension study. Osteoporos Int. 2015;26:2773–2783. - PMC - PubMed

LinkOut - more resources