Differential effects of teriparatide, denosumab and zoledronate on hip structural and mechanical parameters in osteoporosis; a real-life study.

PURPOSE: The aim of this study was to evaluate changes in hip geometry parameters following treatment with teriparatide (TPD), denosumab (Dmab) and zoledronate (ZOL) in real-life setting. METHODS: We studied 249 patients with osteoporosis (OP) with mean [SD] age of 71.5 [11.1] years divided into 3 treatment groups; Group A received TPD; n = 55, Group B (Dmab); n = 116 and Group C (ZOL); n = 78 attending a routine metabolic bone clinic. Bone mineral density (BMD) was measured by DXA at the lumbar spine (LS), total hip (TH) and femoral neck (FN) prior to treatment and after 2 years (Group A), after a mean treatment duration of 3.3 [1.3] years (Group B) and after 1, 2 and 3 doses of ZOL (Group C) to assess treatment response. Hip structural analysis (HSA) was carried out retrospectively from DXA-acquired femur images at the narrow neck (NN), the intertrochanter (IT) and femoral shaft (FS). RESULTS: Changes in parameters of hip geometry and mechanical strength were seen in the following treatment. Percentage change in cross-sectional area (CSA): 3.56[1.6] % p = 0.01 and cross-sectional moment of inertia (CSMI): 4.1[1.8] % p = 0.029 increased at the NN only in Group A. Improvement in HSA parameters at the IT were seen in group B: CSA: 3.3[0.67]% p < 0.001, cortical thickness (Co Th): 2.8[0.78]% p = 0.001, CSMI: 5.9[1.3]% p < 0.001, section modulus (Z):6.2[1.1]% p < 0.001 and buckling ratio (BR): - 3.0[0.86]% p = 0.001 with small changes at the FS: CSA: 1.2[0.4]% p = 0.005, Z:1.6 [0.76]%, p = 0.04. Changes at the IT were also seen in Group C (after 2 doses): CSA: 2.5[0.77]% p = 0.017, Co Th: 2.4[0.84]% p = 0.012, CSMI: 3.9[1.3]% p = 0.017, Z:5.2[1.16]% p < 0.001 and BR: - 3.1[0.88]% p = 0.001 and at the NN (following 3 doses): outer diameter (OD): 4.0[1.4]% p = 0.0005, endocortical diameter(ED): 4.3[1.67% p = 0.009, CSA:5.2[1.8]% p = 0.003, CSMI: 9.3[3.8]% p = 0.019. CONCLUSIONS: Analysis of the effect of OP therapies on hip geometry is useful in understanding the mechanisms of their anti-fracture effect and may provide additional information on their efficacy.

The relationship between circulating adiponectin, leptin and vaspin with bone mineral density (BMD), arterial calcification and stiffness: a cross-sectional study in post-menopausal women.

OBJECTIVE: To explore the relationship between circulating adiponectin, leptin and vaspin with bone mineral density (BMD), arterial stiffness and vascular calcification in post-menopausal women. We hypothesised that adipokines produced by adipose tissue may be mediators of bone and cardiovascular disease (CVD) and explain, in part, the observed association between osteoporosis and CVD. DESIGN: We studied 386 ambulant community dwelling postmenopausal women aged (mean [SD] 61 [6.4] years). BMD at the lumbar spine, femoral neck (FN), and total hip (TH), body composition; fat mass (FM) and lean mass (LM) as well as abdominal aortic calcification (AAC) were determined by dual energy X-ray absorptiometry. Pulse wave velocity (PWV) and augmentation index, markers of arterial stiffness were measured. Fasting adiponectin, leptin and vaspin were quantified in serum. RESULTS: A positive independent association was observed between vaspin and BMD at the FN (p = 0.009), TH (p = 0.037) in the whole study population adjusted for confounders including age, FM, LM and lifestyle variables. Using the same model, a negative association was seen between adiponectin and BMD at the FN in women with osteoporosis (p = 0.043). Serum adiponectin was significantly higher in women with fractures (20.8 [9.3] µg/ml compared to those without (18.5 [8.6] µg/ml, p = 0.018) and associated with a significant increased risk of fracture (HR 1.032, 95% CI 1.003-1.063, p = 0.032). Leptin was not associated with BMD or fracture risk after adjustment. Adiponectin was independently associated with AAC (p = 0.007) and significantly higher in women with AAC scores > 1; (19.2[9.2]) compared to those with no or low AAC scores (<1); 16.8 [8.0], p = 0.018). In adjusted analyses, PWV velocity was positively associated with circulating vaspin (p = 0.039) and AI was negatively associated with serum leptin (p = 0.002). CONCLUSION: Adiponectin, leptin, vaspin are related to markers of bone and vascular health and may contribute to the observed association between osteoporosis and CVD.

Bone Mineral Density and Body Composition are Associated with Circulating Angiogenic Factors in Post-menopausal Women.

Lean mass (LM) and fat mass (FM) are closely related to bone mass (BM) in post-menopausal women, although their relative importance is unclear. Angiogenic factors which control angiogenesis may influence BM, LM and FM. The aim of the study was to compare the contribution of LM and FM to bone mineral density (BMD) and the association between these tissues and circulating angiogenic factors. The study population comprised of 392 post-menopausal women aged mean [SD] 61.8 [6.4] years. BMD was measured at the lumbar spine (LS), neck of femur and total hip (TH) by dual-energy X-ray absorptiometry (DXA). DXA scan was also used to determine LM and FM. Angiopoietin-1 and 2 (ANG-1, ANG-2) were measured by sandwich enzyme-linked immunosorbent assay. Following adjustment for confounders, significant positive independent associations were seen between LM with BMD at all skeletal sites (TH: p < 0.0001) and FM with BMD at the hip sites (TH: p = 0.004). When BMD and LM were regressed against the angiogenic factors, positive associations were seen between ANG-2 with LM (p = 0.002) and LS BMD (p = 0.05). Negative associations were observed between the ratio of ANG-1/ANG-2 with LS BMD (p = 0.014), TH BMD (p = 0.049) and LM (p = 0.029). FM and fat distribution (android/gynoid fat ratio) were negatively associated with ANG-1 (p = 0.006) and ANG-2 (p = 0.004), respectively. ANG-1 and ANG-2 may be involved in the maintenance of bone, muscle and fat mass.