Dataset Information

Effects of Two Years of Teriparatide, Denosumab, or Both on Bone Microarchitecture and Strength (DATA-HRpQCT study).

ABSTRACT: In postmenopausal osteoporosis, combining denosumab and teriparatide increases hip and spine bone mineral density more than either monotherapy.The objective of the study was to determine the effects of 2 years of combination therapy on bone microarchitecture and estimated strength.This was an open-label, randomized controlled trial.We performed high-resolution peripheral quantitative computed tomography at the distal tibia and radius in 94 postmenopausal osteoporotic women randomized to 2 years of teriparatide 20 ?g sc daily, denosumab 60 mg sc every 6 months, or both.Total volumetric bone mineral density (vBMD) at the radius and tibia, trabecular vBMD at the radius, and cortical vBMD at the tibia all increased more in the combination group than both monotherapy groups (P < .002 for all comparisons with combination). Cortical thickness at the tibia also increased more in the combination group (8.1% ± 4.3%) than both other groups (P < .001). Cortical porosity at both the radius and tibia increased progressively over the 24-month treatment period in the teriparatide group but was stable in both other groups (P < .001 teriparatide vs both other groups). Trabecular vBMD at the tibia increased similarly in all groups, whereas radius trabecular vBMD increased more in the combination group than the other groups (P < .01 for both comparisons). Finite element analysis-estimated strength improved or was maintained by all treatments at both the radius and tibia.Two years of combined teriparatide and denosumab improves bone microarchitecture and estimated strength more than the individual treatments, particularly in cortical bone. These findings suggest that this regimen may be beneficial in postmenopausal osteoporosis.

SUBMITTER: Tsai JN

PROVIDER: S-EPMC4870854 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Effects of Two Years of Teriparatide, Denosumab, or Both on Bone Microarchitecture and Strength (DATA-HRpQCT study).

Tsai J N JN Uihlein A V AV Burnett-Bowie S M SM Neer R M RM Derrico N P NP Lee H H Bouxsein M L ML Leder B Z BZ

The Journal of clinical endocrinology and metabolism 20160310 5

<h4>Context</h4>In postmenopausal osteoporosis, combining denosumab and teriparatide increases hip and spine bone mineral density more than either monotherapy.<h4>Objective</h4>The objective of the study was to determine the effects of 2 years of combination therapy on bone microarchitecture and estimated strength.<h4>Design</h4>This was an open-label, randomized controlled trial.<h4>Participants and methods</h4>We performed high-resolution peripheral quantitative computed tomography at the dist ...[more]

PMID: 26964731

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Project description:Combined teriparatide and denosumab increases spine and hip bone mineral density more than either drug alone. The effect of this combination on skeletal microstructure and microarchitecture, however, is unknown. Because skeletal microstructure and microarchitecture are important components of skeletal integrity, we performed high-resolution peripheral quantitative computed tomography (HR-pQCT) assessments at the distal tibia and radius in postmenopausal osteoporotic women randomized to receive teriparatide 20?µg daily (n?=?31), denosumab 60?mg every 6 months (n?=?33), or both (n?=?30) for 12 months. In the teriparatide group, total volumetric bone mineral density (vBMD) did not change at either anatomic site but increased in both other groups at both sites. The increase in vBMD at the tibia was greater in the combination group (3.1?±?2.2%) than both the denosumab (2.2?±?1.9%) and teriparatide groups (-0.3?±?1.9%) (p?<?0.02 for both comparisons). Cortical vBMD decreased by 1.6?±?1.9% at the tibia and by 0.9?±?2.8% at the radius in the teriparatide group, whereas it increased in both other groups at both sites. Tibia cortical vBMD increased more in the combination group (1.5?±?1.5%) than both monotherapy groups (p?<?0.04 for both comparisons). Cortical thickness did not change in the teriparatide group but increased in both other groups. The increase in cortical thickness at the tibia was greater in the combination group (5.4?±?3.9%) than both monotherapy groups (p?<?0.01 for both comparisons). In the teriparatide group, radial cortical porosity increased by 20.9?±?37.6% and by 5.6?±?9.9% at the tibia but did not change in the other two groups. Bone stiffness and failure load, as estimated by finite element analysis, did not change in the teriparatide group but increased in the other two groups at both sites. Together, these findings suggest that the use of denosumab and teriparatide in combination improves HR-pQCT measures of bone quality more than either drug alone and may be of significant clinical benefit in the treatment of postmenopausal osteoporosis.

Project description:In postmenopausal women, 2?yr of combined teriparatide and denosumab increases bone mineral density more than either drug alone, and switching from either combination or teriparatide to denosumab for an additional 2?yr further increases bone mineral density. Conversely, switching from denosumab to teriparatide results in transient bone loss. The effects of these interventions on spine microarchitecture are unknown. In the DATA and DATA-Switch studies, 94 postmenopausal osteoporotic women were randomized to receive 24?mo of teriparatide (20?µg daily), denosumab (60?mg every 6?mo), or both. Then, women originally assigned to 24?mo of teriparatide received 24?mo of denosumab, whereas subjects originally randomized to 24?mo of denosumab received 24?mo of teriparatide. Subjects who received both drugs received an additional 24?mo of denosumab alone. Spine trabecular bone score (TBS, a gray-level textural assessment of bone microarchitecture) was measured blinded from treatment groups using images from 2-dimensional dual-energy X-ray absorptiometry spine scans at 0, 12, 24, 30, 36, and 48?mo in 65 women who had posterior-anterior spine dual-energy X-ray absorptiometry images suitable for TBS analysis. After 24?mo, TBS increased by 2.7?±?4.7% in the teriparatide group (p?=?0.009 vs baseline), by 1.8?±?5.0% in the denosumab group (p?=?0.118 vs baseline), and by 4.5?±?6.7% in the combination group (p?=?0.017 vs baseline), with no significant between-group differences. In the 6?mo after the treatments were switched (months 24-30), TBS continued to increase in the combination-to-denosumab and teriparatide-to-denosumab groups but decreased by -1.1?±?4.0% in the denosumab-to-teriparatide group (p?<?0.05 vs other groups). After 48?mo, compared to month 0, TBS increased by 5.1?±?5.8% in the teriparatide-to-denosumab group, by 3.6?±?4.2% in the denosumab-to-teriparatide group, and by 6.1?±?4.7% in the combination-to-denosumab group (p?<?0.001 vs baseline for all groups, p?=?not significant for between-group differences). Switching from teriparatide to denosumab also increased spine TBS. Conversely, switching from denosumab to teriparatide transiently degraded spine trabecular microarchitecture, the clinical consequences of which require further study.

Project description:BackgroundTo gain insight into how teriparatide affects various bone health parameters, we assessed the effects of teriparatide treatment with use of standard DXA (dual x-ray absorptiometry) technology and two newer technologies, high-resolution MRI (magnetic resonance imaging) and finite element analysis of quantitative CT (computed tomography) scans.MethodsIn this phase-4, open-label study, postmenopausal women with severe osteoporosis received 20 μg/day of teriparatide. Assessments included (1) changes in areal BMD (bone mineral density) (in g/cm2) at the radius, spine, and hip on DXA, (2) changes in volumetric BMD (in mg/cm3) at the spine and hip on quantitative CT scans, (3) changes in bone microarchitecture at the radius on high-resolution MRI, (4) estimated changes in spine and hip strength according to finite element analysis of quantitative CT scans, (5) changes in bone turnover markers in serum, and (6) safety.ResultsThirty-five subjects were enrolled; thirty completed eighteen months and twenty-five completed an optional six-month extension. No significant changes were observed for the primary outcome, high-resolution MRI at the distal aspect of the radius. At month eighteen, the least-squares mean percentage change from baseline in total volumetric BMD at the spine was 10.05% (95% confidence interval [CI], 6.83% to 13.26%; p < 0.001), and estimated spine strength increased 17.43% (95% CI, 12.09% to 22.76%; p < 0.001). Total volumetric BMD at the hip increased 2.22% (95% CI, 0.37% to 4.06%; p = 0.021), and estimated hip strength increased 2.54% (95% CI, 0.06% to 5.01%; p = 0.045). Areal BMD increased at the lumbar spine and femoral neck, was unchanged for the total hip and at the distalmost aspect of the radius, and decreased at a point one-third of the distance between the wrist and elbow. Bone turnover markers increased at months three, six, and twenty-four (all p < 0.05). No unexpected adverse events were observed.ConclusionsHigh-resolution MRI failed to identify changes in bone microarchitecture at the distal aspect of the radius, a non-weight-bearing site that may not be suitable for assessing effects of an osteoanabolic agent. Teriparatide increased areal BMD at the spine and femoral neck and volumetric BMD at the spine and hip. Estimated vertebral and femoral strength also increased. These findings and increases in bone turnover markers through month twenty-four are consistent with the known osteoanabolic effect of teriparatide.Level of evidenceTherapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Project description:Current osteoporosis medications increase bone mineral density (BMD) modestly and reduce, but do not eliminate, fracture risk. Attempts to improve efficacy by administering anabolic agents and bisphosphonates concomitantly have been unsuccessful. Conversely, 12 months of concomitant denosumab and teriparatide therapy increases BMD more than either drug alone.The purpose of this study was to determine whether 24 months of combined denosumab and teriparatide will increase hip and spine BMD more than either individual agent.Preplanned continuation of the Denosumab and Teriparatide Administration (DATA) randomized controlled trial in which postmenopausal osteoporotic women received teriparatide (20 ?g daily), denosumab (60 mg every 6 months), or both medications for 24 months.Participants were 94 postmenopausal women with osteoporosis.Lumbar spine, femoral neck, total hip, and distal radius BMD and serum markers of bone turnover were measured.At 24 months, lumbar spine BMD increased more in the combination group (12.9 ± 5.0%) than in either the teriparatide (9.5 ± 5.9%, P = .01) or denosumab (8.3 ± 3.4%, P = .008) groups. Femoral neck BMD also increased more in the combination group (6.8 ± 3.6%) than in either the teriparatide (2.8 ± 3.9%, P = .003) or denosumab (4.1 ± 3.8%, P = .008) groups. Similarly, total hip BMD increased more in the combination group (6.3 ± 2.6%) than in the teriparatide (2.0 ± 3.0%) or denosumab (3.2 ± 2.5%) groups (P < .001 for both). Although spine and hip BMD continued to increase in the second year in all groups, these year 2 increases did not differ among groups. Serum C-telopeptide and N-terminal propeptide of type 1 procollagen were equally suppressed in the denosumab and combination groups, whereas osteocalcin decreased more in the denosumab group than in the combination group, a difference that persisted, but lessened, in the second year of therapy.Two years of concomitant teriparatide and denosumab therapy increases BMD more than therapy with either medication alone and more than has been reported with any current therapy. The combination of these agents may prove to be an important treatment option in patients at high risk of fracture.

Project description:BackgroundPatients with rheumatoid arthritis (RA) are at increased risk of fractures. Although their decline in bone mineral density (BMD) is well-established, data regarding the alterations in bone microarchitecture are limited. In this study, we aimed to evaluate bone microarchitecture, geometry, and volumetric BMD among patients with RA in mainland China using high-resolution peripheral quantitative computed tomography (HRpQCT).MethodsIn this cross-sectional study, patients with RA were recruited from the Peking Union Medical College Hospital site of the Chinese Registry of rhEumatoiD arthrITis (CREDIT). Each participant underwent HRpQCT scanning (Scanco XtremeCT II), thoracolumbar X-ray and dual-energy X-ray absorptiometry. The primary outcomes were HRpQCT-related measures at distal radius and tibia. Data regarding demographic features, RA-related characteristics, and history of fragility fractures were collected. Correlation between HRpQCT parameters and potentially related factors were analyzed using linear regression analysis. A group of age- and sex-matched healthy controls was included for comparison.ResultsA total of 81 patients with RA [69 women, aged 57.9 ± 8.7 years, disease duration 5.7 (IQR 1.4-11.2) years] and 81 matched healthy controls were included. Compared with controls, patients with RA had significantly larger bone area and lower total and trabecular vBMD at both the distal radius and tibia. Lower cortical bone thickness was also shown at the distal tibia. Among patients with RA, advanced age, low BMI, female sex, disease duration, and activity were associated with decreased vBMD and impaired bone microstructure. Female reproductive factors including menopause, late menarche, breast feeding, and early childbirth also showed negative correlation with these parameters. Compared to patients with RA without fractures, patients with fragility fractures (n = 11) showed lower trabecular and cortical vBMD, thinner cortical bone, impaired trabecular microstructure, and a trend of declined bone strength. Current glucocorticoid intake was related to decreased vBMD, trabecular number, increased trabecular separation, and inhomogeneity.ConclusionsIn this study, we observed alterations in bone mineral density, geometry, and microarchitecture among patients with RA compared to healthy individuals, which may impair bone strength and lead to increased risk of fractures. Both traditional risk factors for osteoporosis and RA-associated factors need to be considered in the assessment of the bone quality.

Project description:Accelerated bone loss (ABL) shown on routine dual-energy X-ray absorptiometry (DXA) may be accompanied by microarchitectural changes, increased cortical porosity, and lower bone strength. To test this hypothesis, we performed a cross-sectional study and used high-resolution peripheral quantitative computed tomography (HR-pQCT) scans (Scanco Medical AG, Brüttisellen, Switzerland) to measure estimated bone strength and microarchitecture in the distal radius and distal and diaphyseal tibia. We studied 1628 men who attended the year 14 exam of the Osteoporotic Fractures in Men (MrOS) study. We retrospectively characterized areal bone mineral density (aBMD) change from the year 7 to year 14 exam in three categories: "accelerated" loss, ?10% loss at either the total hip or femoral neck (n?=?299, 18.4%); "expected" loss, <10% (n?=?1061, 65.2%), and "maintained" BMD, ?0% (n?=?268, 16.5%). The ABL cut-off was a safety alert established for MrOS. We used regression models to calculate adjusted mean HR-pQCT parameters in men with ABL, expected loss, or maintained BMD. Men who experienced ABL were older and had a lower body mass index and aBMD and experienced greater weight loss compared with other men. Total volumetric BMD and trabecular and cortical volumetric BMD were lower in men with ABL compared with the expected or maintained group. Men with ABL had significantly lower trabecular bone volume fraction (BV/TV), fewer trabeculae, and greater trabecular separation at both the distal radius and tibia than men with expected loss or who maintained aBMD, all p trend <0.001. Men with ABL had lower cortical thickness and lower estimated bone strength, but there was no difference in cortical porosity except at the tibia diaphyseal site. In summary, men with ABL have lower estimated bone strength, poorer trabecular microarchitecture, and thinner cortices than men without ABL but have similar cortical porosity. These impairments may lead to an increased risk of fracture. © 2018 American Society for Bone and Mineral Research.

Dataset Information

Effects of Two Years of Teriparatide, Denosumab, or Both on Bone Microarchitecture and Strength (DATA-HRpQCT study).

Publications

Effects of Two Years of Teriparatide, Denosumab, or Both on Bone Microarchitecture and Strength (DATA-HRpQCT study).

Similar Datasets

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