CONCLUSION Estrogen with an osteoblast P4R-acting progestin ( EPT ) in these five published RCT provides Level 1 evidence that MPA caused significantly greater annual percent spinal BMD gains than the same dose of ET .
OBJECTIVE To assess whether progesterone ( P4 ) or osteoblast P4 receptor-acting progestin ( P ) contributed to estrogen ( E ) therapy-related  increased areal bone mineral density ( BMD ) in r and omized controlled trials ( RCT ) with direct r and omization to estrogen ( ET ) or estrogen-progestin ( EPT ) therapy .
Effects of intravenous zoledronic acid plus subcutaneous teriparatide [rhPTH(1-34)] in postmenopausal osteoporosis.
Clinical data suggest concomitant therapy with bisphosphonates and parathyroid hormone ( PTH ) may blunt the anabolic effect of PTH ; rodent models suggest that infrequently administered bisphosphonates may interact differently . To evaluate the effects of combination therapy with an intravenous infusion of zoledronic acid 5 mg and daily subcutaneous recombinant human (rh)PTH(1 - 34 ) ( teriparatide ) 20 µg versus either agent alone on bone mineral density ( BMD ) and bone turnover markers , we conducted a 1-year multicenter , multinational , r and omized , partial double-blinded , controlled trial . 412 postmenopausal women with osteoporosis ( mean age 65 ± 9 years ) were r and omized to a single infusion of zoledronic acid 5 mg plus daily subcutaneous teriparatide 20 µg ( n = 137 ) , zoledronic acid alone ( n = 137 ) , or teriparatide alone ( n = 138 ) . The primary endpoint was percentage increase in lumbar spine BMD ( assessed by dual-energy X-ray absorptiometry [ DXA ] ) at 52 weeks versus baseline . Secondary endpoints included change in BMD at the spine at earlier time points and at the total hip , trochanter , and femoral neck at all time points . At week 52 , lumbar spine BMD had increased 7.5 % , 7.0 % , and 4.4 % in the combination , teriparatide , and zoledronic acid groups , respectively ( p < .001 for combination and teriparatide versus zoledronic acid ) . In the combination group , spine BMD increased more rapidly than with either agent alone ( p < .001 versus both teriparatide and zoledronic acid at 13 and 26 weeks ) . Combination therapy increased total-hip BMD more than teriparatide alone at all times ( all p < .01 ) and more than zoledronic acid at 13 weeks ( p < .05 ) , with final 52-week increments of 2.3 % , 1.1 % , and 2.2 % in the combination , teriparatide , and zoledronic acid groups , respectively . With combination  therapy , bone formation ( assessed by serum N-terminal propeptide of type I collagen [ PINP ] ) increased from 0 to 4 weeks , declined minimally from 4 to 8 weeks , and then rose throughout the trial , with levels above baseline from 6 to 12 months . Bone resorption ( assessed by serum β-C-telopeptide of type I collagen [ β-CTX ] ) was markedly reduced with combination therapy from 0 to 8 weeks ( a reduction of similar magnitude to that seen with zoledronic acid alone ) , followed by a gradual increase after week 8 , with levels remaining above baseline for the latter half of the year . Levels for both markers were significantly lower with combination therapy versus teriparatide alone ( p < .002 ) . Limitations of the study included its short duration , lack of endpoints beyond DXA-based BMD ( e.g. , quantitative computed tomography and finite-element modeling for bone strength ) , lack of teriparatide placebo , and insufficient power for fracture outcomes . We conclude that while teriparatide increases spine BMD more than zoledronic acid and zoledronic acid increases hip BMD more than teriparatide , combination therapy provides the largest , most rapid increments when both spine and hip sites are considered
CONCLUSION Estrogen with an osteoblast P4R-acting progestin ( EPT ) in these five published RCT provides Level 1 evidence that MPA caused significantly greater annual percent spinal BMD gains than the same dose of ET .
OBJECTIVE To assess whether progesterone ( P4 ) or osteoblast P4 receptor-acting progestin ( P ) contributed to estrogen ( E ) therapy-related  increased areal bone mineral density ( BMD ) in r and omized controlled trials ( RCT ) with direct r and omization to estrogen ( ET ) or estrogen-progestin ( EPT ) therapy .