Clinical trial NCT02435147: Longitudinal Effects of Denosumab on Trabecular Bone Score and Femur Strength Index
Official title: Longitudinal Effects of Denosumab on Trabecular Bone Score and Femur Strength Index
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Osteoporosis
Bone Fracture
Lead sponsor: HealthEast Care System
Sponsor class: OTHER
Collaborators: name: Amgen
First posted: 2015-05-06
Enrollment: 86
Sex: FEMALE
Minimum age (years): 40
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This study will enroll postmenopausal women between the ages of 40 and 90 years who have completed a minimum of 36 months of denosumab therapy for the treatment of osteoporosis.

Brief summary: The purpose of this study is to validate the long-term benefit of denosumab for osteoporosis treatment in a real-world clinical practice setting. We hypothesize that continued therapy (36+months) with denosumab will increase both trabecular bone score (TBS) and femur strength index (FSI) and reduce fracture and other bone health risks among post-menopausal women with osteoporosis.

Detailed description: Bone fractures are a major cause of morbidity and health care expense among patients with osteoporosis.The goal of osteoporosis therapy is to reduce fracture risk. The administration of denosumab 60 mg subcutaneously (SC) every six months has been shown to limit bone turnover, increase bone mineral density (BMD), and reduce the risk for new vertebral, non-vertebral, and hip fractures among postmenopausal women with osteoporosis (Cummings, 2009). Although BMD is an important factor for fracture risk, it does not describe bone microarchitecture, which is related to bone quality and mechanical bone strength. Trabecular bone score (TBS) is an index for bone microarchitecture extracted from anterior-posterior spine dual-energy X-ray absorptiometry (DXA). Previous research has shown TBS to differentiate between women with and without fractures as well as predict future fracture even after adjustment for BMD (Simonelli, Leib, Winzenrieth, \& Hans, 2012). In a study of 29,407 Canadian women age 50 years and older at the time of baseline hip and spine DXA, health service records were assessed to determine the incidence of non-traumatic osteoporotic fractures subsequent to BMD testing. Lumbar spine TBS was derived for each DXA examination and blinded to clinical parameters and outcomes. Osteoporotic fractures were identified in 1668 (5.7%) women, including 439 (1.5%) spine and 293 (1.0%) hip fractures. Significantly lower spine TBS and BMD were found in women with major osteoporotic, spine, and hip fractures (p\<0.0001). The results of this study suggest that spine TBS is predictive of osteoporotic fractures and provides additional clinical information independent of spine and hip BMD; therefore, combining TBS trabecular texture index with BMD incrementally improves fracture prediction in postmenopausal women (Hans, Goertzen, Krieg, \& Leslie, 2011).

Clinical research has demonstrated the positive effect of denosumab on TBS over time. In a randomized, double-blind, placebo-controlled trial of 215 postmenopausal women with low BMD at the spine or total hip, denosumab (60mg SC every 6 months) was found to increase lumbar spine QCT, DXA, and TBS at 12 months compared to placebo or alendronate (Thomas, 2013). In another study conducted by McClung et al, postmenopausal women with osteoporosis who received denosumab were found to have significant increases in TBS, independent of BMD, at 36 months compared to baseline and placebo (McClung, Lippuner, Brandi, Kaufman, Zanchetta, \& Krieg, 2012).

Femur strength index (FSI), which is a measure of femoral bone density, structure, and strength, has also been shown to predict hip fracture independent of bone density and hip axis length. In a study which compared FSI in a group of women age 50 years and older with and without hip fracture (365 with prior hip fracture and 2,141 controls), FSI was found to be significantly lower in the fracture group, after adjusting for T score and hip axis length (Faulkner, et al., 2006). Like TBS, FSI can be obtained from femur DXA measurements using modern software.

This is a single-site, open-label, non-randomized, observational study designed to assess the change in TBS and FSI at 36 months. among post-menopausal women with osteoporosis taking denosumab. All patients included in this study are under the medical care of the principal investigator. Subjects will enter the study once they have completed 36 months of treatment with denosumab and have evaluable DXA scans. Medical records will be retrospectively reviewed and percent change in TBS and FSI scores will be calculated.

Eligibility criteria: Inclusion Criteria:

* Subjects must meet the following inclusion criteria to be eligible for study entry:

  * Post-menopausal female with diagnosed osteoporosis
  * Age 40-90 years
  * Completed 36 months of denosumab therapy (SQ; 60mg every 6 months) but not yet received the 42 month injection
  * Availability of DXA scans at the study-required time points, including the willingness of subjects to undergo a DXA evaluation at 36 months, if required
  * Provided written informed consent

Exclusion Criteria:

* Patients will be excluded from this study for any of the following reasons:

  * Received denosumab injections for less than 36 months
  * Patients who have missed more than 1 dose of denosumab in a 36 month period
  * Contra-indicated for treatment with denosumab
  * History of rheumatoid arthritis
  * Current diagnosis of hyperparathyroidism; hyperthyroidism; osteomalacia, or other known diseases that can affect bone
  * In the opinion of the investigator, have any kind of disorder that may compromise the ability of the subject to provide written informed consent

Primary outcomes:
measure: Proportion of Change in Mean Trabecular Bone Score
timeFrame: Baseline and 36 months
Secondary outcomes:
measure: Proportion of Change in Mean Femur Strength Index Score
timeFrame: Baseline and 36 months
Other outcomes:
Locations:
city: Saint Paul
country: United States
facility: HealthEast Care System
state: Minnesota
Study officials:
affiliation: HealthEast Care System
name: Christine Simonelli, MD
role: PRINCIPAL_INVESTIGATOR
References: