title: Postmenopausal women treated with combination parathyroid hormone (1-84) and ibandronate demonstrate different microstructural changes at the radius vs. tibia: the PTH and Ibandronate Combination Study (PICS).
abstract: CONCLUSIONS
  In postmenopausal women receiving combination parathyroid hormone (PTH) (1-84) therapy and ibandronate, we evaluated bone microarchitecture and biomechanics using high-resolution peripheral quantitative computed tomography (HR-pQCT). Cortical and trabecular changes were different at the nonweight-bearing radius vs. the weight-bearing tibia, with more favorable overall changes at the tibia.
  
  
  BACKGROUND
  PTH therapy and bisphosphonates decrease fracture risk in postmenopausal osteoporosis, but their effects on bone microstructure and strength have not been fully characterized, particularly during combination therapy. PTH increases trabecular bone mineral density (BMD) substantially but may decrease cortical BMD, possibly by stimulating intracortical remodeling. We evaluated bone microarchitecture and biomechanics with HR-pQCT at the radius (a nonweight-bearing site) and tibia (weight bearing) in women receiving combination PTH(1-84) and ibandronate.
  
  
  METHODS
  Postmenopausal women with low bone mass (n = 43) were treated with 6 months of PTH(1-84) (100 μg/day), either as one 6- or two 3-month courses, in combination with ibandronate (150 mg/month) over 2 years. HR-pQCT was performed before and after therapy.
  
  
  RESULTS
  Because changes in HR-pQCT parameters did not differ between treatment arms, groups were pooled into one cohort for analysis. Trabecular BMD increased at both radius and tibia (p < 0.01 for each). Cortical thickness and BMD decreased at the radius (p < 0.01), consistent with changes in dual-energy X-ray absorptiometry, while these parameters did not change at the tibia (p ≤ 0.02 for difference between radius and tibia). In contrast, cortical porosity increased at the tibia (p < 0.01) but not radius. Stiffness and failure load decreased at the radius (p < 0.0001) but did not change at the tibia.
  
  
  CONCLUSIONS
  Cortical and trabecular changes in response to the PTH/ibandronate treatment combinations utilized in this study were different at the nonweight-bearing radius vs. the weight-bearing tibia, with more favorable overall changes at the tibia. Our findings support the possibility that weight bearing may optimize the effects of osteoporosis therapy.
authors.affiliation: Endocrine Research Unit, San Francisco Veterans Affairs Medical Center, 4150 Clement Street, 111N, San Francisco, CA, 94121, USA, anne.schafer@ucsf.edu.
authors.forename: A L
authors.initials: AL
authors.lastname: Schafer
authors.forename: A J
authors.initials: AJ
authors.lastname: Burghardt
authors.forename: D E
authors.initials: DE
authors.lastname: Sellmeyer
authors.forename: L
authors.initials: L
authors.lastname: Palermo
authors.forename: D M
authors.initials: DM
authors.lastname: Shoback
authors.forename: S
authors.initials: S
authors.lastname: Majumdar
authors.forename: D M
authors.initials: DM
authors.lastname: Black
mesh_terms: D015502:Absorptiometry, Photon; D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004164:Diphosphonates / Q000494:pharmacology* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D020342:Finite Element Analysis; D006801:Humans; D000077557:Ibandronic Acid; D055118:Medication Adherence; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy / Q000503:physiopathology; D010281:Parathyroid Hormone / Q000494:pharmacology* / Q000627:therapeutic use; D011884:Radius / Q000187:drug effects* / Q000503:physiopathology; D013977:Tibia / Q000187:drug effects* / Q000503:physiopathology; D014057:Tomography, X-Ray Computed / Q000379:methods; D016474:Weight-Bearing / Q000502:physiology
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D010281:Parathyroid Hormone; D000077557:Ibandronic Acid