Original ArticleResponse to Therapy With Teriparatide, Denosumab, or Both in Postmenopausal Women in the DATA (Denosumab and Teriparatide Administration) Study Randomized Controlled Trial
Introduction
Dual-energy X-ray absorptiometry (DXA)-derived bone mineral density (BMD) is a surrogate marker commonly monitored to assess an individual patient's response to osteoporosis therapy. Decisions regarding continuing therapy or switching to an alternative drug are often made on the basis of changes in BMD over time (1). Two of our most potent osteoporosis medications, the osteoanabolic agent, teriparatide, and the antiresorptive agent, denosumab, increase spine and hip BMD significantly and reduce the risk of vertebral and nonvertebral fractures 2, 3 Moreover, with both of these agents, the magnitude of the BMD improvements has been shown to predict the observed reduction in fracture incidence, though to varying degrees 4, 5. In the DATA study, we recently reported that 2 yr of combined denosumab and teriparatide increases BMD at the hip and spine more than either drug alone and more than can be achieved with any currently available agent 6, 7. To assess the variability of the response to combination therapy, we now compare the individual response rates in women treated with denosumab, teriparatide, or both medications at the total hip (TH), femoral neck (FN), lumbar spine (LS), and distal 1/3 radius.
Section snippets
Subjects and Methods
The details of the DATA study design and subjects have been described previously 6, 7. Ninety-four postmenopausal women aged 45 or older were recruited through targeted mailings, advertisements, and physician referrals. Subjects were required to be at least 36 mo since last menses (or since hysterectomy if follicle-stimulating hormone (FSH) level >40 U/L) and at high fracture risk, defined as a BMD T-score ≤−2.5 at the spine, hip, or FN; a T-score ≤−2.0 with at least 1 BMD-independent risk
Results
The baseline characteristics of the 82 subjects completing all visits are shown in Table 1, as are the 2-yr mean percent changes in BMD achieved in each treatment group. As reported previously, after 24 mo, LS BMD increased more in women receiving both drugs (12.9 ± 5.0%) than both the teriparatide (9.5 ± 5.9%, p = 0.01) and denosumab (8.3 ± 3.4%, p = 0.008) groups. FN BMD also increased more in the combination group (6.8 ± 3.6%) than both the teriparatide (2.8 ± 3.9%, p = 0.003) and denosumab
Discussion
In the present study, we have demonstrated that a greater proportion of postmenopausal osteoporotic women treated with 24 mo of combined denosumab and teriparatide experience meaningful improvement in hip and spine BMD than those treated with either teriparatide or denosumab alone. Moreover, not only are the response rates for combined denosumab and teriparatide higher than those reported for the individual agents in the present study, but also when compared to prior studies of other
Acknowledgments
We wish to thank Dr. John Potts for his consistent advice and support, the staff at the MGH Bone Density Center, and our dedicated study volunteers.
Funding sources: This study was supported by Eli Lilly Inc. and Amgen Inc. (Grant Number 1 UL1 RR025758-04). Neither Eli Lilly nor Amgen had any role in the study design or data analysis, or data interpretation.
References (25)
- et al.
Teriparatide and denosumab, alone or combined, in women with postmenopausal osteoporosis: the DATA study randomised trial
Lancet
(2013) - et al.
Importance of precision in bone density measurements
J Clin Densitom
(2001) - et al.
Femoral strength in osteoporotic women treated with teriparatide or alendronate
Bone
(2012) - et al.
American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the diagnosis and treatment of postmenopausal osteoporosis
Endocr Pract
(2010) - et al.
Impact of osteoporosis treatment adherence on fracture rates in North America and Europe
Am J Med
(2009) - et al.
Are osteoclasts needed for the bone anabolic response to parathyroid hormone? A study of intermittent parathyroid hormone with denosumab or alendronate in knock-in mice expressing humanized RANKL
J Biol Chem
(2010) - et al.
Effects of one year daily teriparatide treatment on trabecular bone material properties in postmenopausal osteoporotic women previously treated with alendronate or risedronate
Bone
(2011) - Adult Official Position of the International Society of Clinical Densitometry 2015 Update....
- et al.
Denosumab for prevention of fractures in postmenopausal women with osteoporosis
N Engl J Med
(2009) - et al.
Effect of parathyroid hormone (1–34) on fractures and bone mineral density in postmenopausal women with osteoporosis
N Engl J Med
(2001)
Change in lumbar spine BMD and vertebral fracture risk reduction in teriparatide-treated postmenopausal women with osteoporosis
J Bone Miner Res
Relationship between bone mineral density changes with denosumab treatment and risk reduction for vertebral and nonvertebral fractures
J Bone Miner Res
Cited by (25)
Bone mineral density response rates are greater in patients treated with abaloparatide compared with those treated with placebo or teriparatide: Results from the ACTIVE phase 3 trial
2019, BoneCitation Excerpt :A responder was defined as a patient with a gain in BMD at all 3 anatomic sites. The >3% threshold was chosen based on dual-energy x-ray absorptiometry (DXA) scanner precision of approximately 1% corresponding to the LSC in BMD at the 95% confidence limits of 3% and to conform with responder analyses performed in other studies of drugs to treat osteoporosis [6,9–14]. BMD was measured by DXA on approved scanners (Hologic, Bedford, MA, or GE Healthcare Lunar, Madison WI), and for each patient, the same scanner was used for all evaluations of BMD.
Effects of Roux-en-Y gastric bypass and sleeve gastrectomy on bone mineral density and marrow adipose tissue
2017, BoneCitation Excerpt :Areal bone mineral density (aBMD, g/cm2) of the lumbar spine (L1–L4), total hip and femoral neck was assessed using DXA (QDR Discovery, Hologic, Inc., Bedford, MA). We have previously established that the same-day in vivo scanning precision at our center is 0.007, 0.008, and 0.012 g/cm2 for PA spine, total hip, and femoral neck, respectively [26]. If necessary, manual retraction of pannus overlying the proximal femur was performed during hip measurements.
Proceedings of the 2019 Santa Fe Bone Symposium: New Concepts in the Care of Osteoporosis and Rare Bone Diseases
2020, Journal of Clinical DensitometryCitation Excerpt :With denosumab inhibiting the pathway that teriparatide depends upon for its catabolic actions, namely RANKL, the dual anabolic/catabolic pathways of teriparatide are perturbed, such that teriparatide is shunted preferentially into its antisclerostin, anabolic pathway. While only a hypothesis, the data from Leder et al appear to support it (33–37). They have clearly shown that this approach has therapeutic merit with regard to greater increases in bone density with combination teriparatide/denosumab therapy vs monotherapy with either agent.
Osteoporosis, bone mineral density and CKD-MBD (II): Therapeutic implications
2019, NefrologiaCitation Excerpt :Denosumab (DMab) is a monoclonal antibody that acts by blocking the ligand receptor of nuclear factor kappa-B (RANKL) and as a consequence inhibits osteoclastogenesis101,102 (Table 4). DMab is useful in the prevention of vertebral, non-vertebral and hip fractures in the general population.101,103,104 The metabolism or excretion of DMab does not depend on renal function and it does not appear to alter renal function, so there are neither dosage adjustments needed nor use restrictions in patients with CKD and/or decreased GFR.14,105
A Delphi consensus on the management of Spanish patients with osteoporosis at high risk of fracture: OSARIDELPHI study
2023, Archives of Osteoporosis
Conflict of interest: BZL has served as a consultant for Eli Lilly, Amgen and Merck. RMN JNT SMB AVU and PMW report no conflict of interest.