Effect of Hormone Replacement, Alendronate, or Combination Therapy on Hip Structural Geometry: A 3-Year, Double-Blind, Placebo-Controlled Clinical Trial

Abstract

This study examined the effect of hormone replacement, alendronate, or combination therapy on hip structural geometry in 373 postmenopausal women over 3 years. We found that antiresorptive agents alone or in combination result in improvement in parameters of hip structural geometry and BMD. These data provide additional information regarding potential mechanisms for fracture reduction with antiresorptive therapy.Introduction: Fracture reduction is only partially explained by increased BMD. The aim of this study was to examine changes in structural geometry of the hip, derived from DXA in postmenopausal women after treatment with antiresorptive agents. Materials and Methods:This was a double-blind, placebo-controlled, randomized clinical trial of 373 women over the age of 65 years, who were randomized to hormone replacement therapy, alendronate, combination therapy, or placebo for 3 years. The outcomes included the DXA-derived hip structure analysis program by Beck, which is an engineering interpretation of the DXA data. The indices included cross-sectional area, section modulus (a measure of bending strength), outer diameter, cortical thickness, and buckling ratio (an index of cortical bone stability). Properties were measured in cross-sectional regions traversing the femur at the narrowest point on the femoral neck, the intertrochanteric region, and the proximal shaft. Results: In the femoral neck, improvement in the hip structure analysis indices were generally significantly greater with combination therapy than either monotherapy; increases were also greater at the intertrochanter compared with hormone replacement therapy. For example, the section modulus at the intertrochanter and narrow neck increased 10.6% and 10.3%, respectively, with combination therapy, 9.1% and 7.3% with alendronate, 5.8% and 6.9% with hormone replacement therapy, and 3.4% and 3.2% with placebo (p < 0.01 across the four groups). Buckling ratio increased, suggesting decreased stability in the placebo group, whereas there was either no change or significant improvements (p < 0.05) in each active treatment group. Conclusions: We conclude that changes in the distribution of bone mass underlying the improvements in density with antiresorptive agents in combination or alone have positive effects on structural strength and stability at the proximal femur. This study provides additional information on the potential mechanisms for fracture reduction with antiresorptive agents.

Proximal hip geometry is linked to several chromosomal regions: Genome-wide linkage results from the Framingham Osteoporosis Study

“…The cross-sectional indices we studied are applicable only to a plane of a DXA image. However, proximal hip geometry obtained by the above method is widely used to understand femoral structure and strength [56,57] and has been shown to predict osteoporotic fragility in several epidemiological studies [8,58,59]. …”

Estrogen therapy for postmenopausal osteoporosis

“…In the estrogen treated subjects, there was an increase of 5.8% and 6.9% in the section modulus at the intertrochanter and narrow neck. The authors suggest that these types of measurements may contribute to the fracture risk reduction with treatment (37).…”

Effects of combination therapy of alendronate and hormonal therapy on bone mineral density in postmenopausal Korean women: A multicenter, randomized controlled clinical trial

“…Moreover, no impairment of bone quality by combining bisphosphonates with HT was found from bone morphometry data (34). Importantly, improvements in the hip structure analysis indices were significantly greater with combination therapy than with either HT or ALEN monotherapy (36), which suggests a mechanism for potential fracture reduction. From these aspects, longterm data including fracture risk and adverse events are necessary to define the exact role of combination therapy.…”