Longitudinal Effects of Denosumab on Trabecular Bone Score and Femur Strength Index
Condition: Osteoporosis; Bone Fracture
MeSH terms: Osteoporosis; Fractures, Bone
Study type: Observational

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.
    

Intervention name(s): denosumab
Intervention type(s): Drug
Intervention description(s): Patients will receive denosumab 60 mg subcutaneously every six months as part of their standard osteoporosis treatment.
Other intervention name(s): Prolia
Intervention MeSH terms: Denosumab
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.