Literature review: The effects of teriparatide therapy at the hip in patients with osteoporosis

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Abstract

Teriparatide is a skeletal anabolic treatment for patients with osteoporosis at high risk for fracture. Because adequate clinical trials have not yet been conducted to assess the efficacy of teriparatide for reducing the risk of hip fracture, we review here the literature regarding how treatment with teriparatide affects the hip in patients with osteoporosis. Teriparatide increases cancellous bone volume, improves bone architecture, and - uniquely among osteoporosis treatments - increases cortical thickness and cortical porosity. By bone scan and positron emission tomography, teriparatide increases bone formation throughout the skeleton, including the hip. Consistent with these findings, studies using dual-energy X-ray absorptiometry and quantitative computed tomography for longitudinal assessment of changes at the hip have consistently shown increases in areal and volumetric bone mineral density, cortical thickness, and finite element-estimated hip strength in patients treated with teriparatide. Finally, in clinical fracture-outcome trials, treatment with teriparatide has been shown to reduce the risk of nonvertebral fracture, a composite endpoint that includes hip fracture. Taken together, this body of evidence suggests that teriparatide positively affects the hip in patients with osteoporosis. © 2014 Elsevier Inc.

Figures

  • Fig. 1. Systematic literature review.
  • Fig. 2. Previously unpublished micro-computed tomography images of paired iliac crest bone biopsies in postmenopausal women with osteoporosis who participated in the Fracture Prevention Trial. Baseline (pre-treatment) is shown on the left; post-treatment with teriparatide is shown on the right. Patient A) aged 59 and treated for 21 months, Patient B) aged 63 years and treated for 18 months, and Patient C) aged 62 and treated for 22 months. Treatment with teriparatide resulted in increases in cortical thickness, cancellous bone volume, and connectivity, aswell as the conversion of rods to plates [12]. These patients had increases in BMD frombaseline representative of the overall group of patients treatedwith teriparatide; increases at the femoral neck BMD were 3.2% for Patient A, 3.2% for Patient B, and a 1.4% for Patient C. Images used with permission of Yebin Jiang.
  • Fig. 3. Paired iliac crest biopsy images from 2 postmenopausal womenwith osteoporosis treated with teriparatide showing pre-treatment and post-treatment findings. These biopsy images are from the studypublished byMa et al. [25]. Thefirst pair of biopsies is from apatient previously treatedwith alendronate and switched to teriparatide. The second pair of biopsies is from an osteoporosis drug naïve patient subsequently treatedwith teriparatide. Overall bone formation increased as indicated by the increase in tetracycline labeling. An increase in intracortical remodeling (cortical porosity) is shown with double labeling indicative of remodeling of older to newer bone. This increase in cortical porosity is accompanied by periosteal and endosteal labeling and an increase in cortical thickness. The biopsy images in panel A are reprinted from Bone, Effects of Teriparatide on Cortical Histomorphometric Variables in PostmenopausalWomenWith orWithout Prior Alendronate Treatment,MaYanfei L., ZengQingQ., ChiangAlanY., BurrDavid, Li Jiliang, DobnigHarald, Fahrleitner-PammerAstrid,Michalská Dana, Marin Fernando, Pavo Imre, Stepan Jan J., 2013, doi: 10.1016/j.bone.2013.11.011, with permission from Elsevier. The biopsy images in panel B are previously unpublished.
  • Fig. 4. Cortical thicknessmaps showing severe osteoporosis and the increase in thickness following teriparatide treatment. (A) Baseline cortical thicknessmaps with medial, superior and posterior views of the femur showing thicker bone (blue/green) at sites of loading including A) inferomedial cortex and B) the calcar femorale regions. Also shown is thin, sub-millimeter cortex (pink/red) at key fracture sites including C) the subcapital superior neck region. Also labeled are the insertion sites of keymuscles of locomotion; D) gluteusmedius, E) psoasmajor and F) quadratus femoris (on the interotrochanteric crest). (B) Post-treatment percentage change and (C) statistical significancemapswhich together indicate regeneration of bone at A), B), C), D), E), and F). Reprinted from Poole KES, Treece GM, Ridgway GR, Mayhew PM, Borggrefe J, et al. (2011) Targeted regeneration of bone in the osteoporotic human femur. PLoS ONE 6(1): e16190. doi:10.1371/journal.pone.0016190.
  • Fig. 5. Proportion of patients experiencing nonvertebral fragility fractures in (A) the Fracture Prevention Trial [97] and (B) the treatment phase of the DANCE observational study [92]. (C) The incidence of hip fractures in the DANCE study (previously unpublished data). N = number of patients in each treatment group at risk × 100; n = number of fractures; NVFX = nonvertebral fragility fracture; and TPTD20 = teriparatide 20 μg/day. In the Fracture Prevention Trial, the relative hazard of NVFX decreased by 7.3% for each additional month of teriparatide 20 μg versus placebo (p = 0.009). In the DANCE study, p values are derived from a one-sample binomial proportion test vs. the first period incidence rate (reference).

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APA

Eriksen, E. F., Keaveny, T. M., Gallagher, E. R., & Krege, J. H. (2014). Literature review: The effects of teriparatide therapy at the hip in patients with osteoporosis. Bone. Elsevier Inc. https://doi.org/10.1016/j.bone.2014.07.014

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