Combination treatment with estrogen and calcitriol in the prevention of age-related bone loss

Estrogen deficiency and declining calcium absorption due to reduced calcitr iol levels or intestinal resistance to calcitriol, are important factors in the pathogenesis of age-related bone loss. The main objective of this stud y was to examine the effect of estrogen and 1,25-dihydroxyvitamin D therapy given individually or in combination on bone loss in elderly women. Four h undred eighty-nine elderly women with normal bone density for their age, ag ed 65-77 yr, were entered into a randomized double blind, placebo-controlle d trial. Women were randomized to one of four groups: conjugated estrogens (0.625 mg , daily) to women without a uterus (estrogen replacement therapy) plus medr oxyprogesterone acetate (2.5 mg, daily) to women with a uterus (hormone rep lacement therapy), calcitriol (0.25 mug twice daily), a combination of horm one replacement therapy/estrogen replacement therapy plus calcitriol, or pl acebos for 3 yr. The primary outcome was the change in bone mineral density of the femoral n eck and spine. In the intent to treat analysis, hormone therapy (hormone re placement therapy/estrogen replacement therapy) produced a mean (+/- 1 SD) increase in bone mineral density of 2.98% (+/-5.45%) at the femoral neck (P < 0.0001) and 4.36% (+/-6.42%) at the spine (P < 0.0001). There were paral lel increases in total hip and trochanter bone mineral density. Calcitriol increased bone mineral density 0.10% (+/- 4.27%) at the femoral neck (P = 0 .57) and 1.65% (+/- 4.83%) at the spine (P < 0.0124). The combination of ho rmone replacement therapy/estrogen replacement therapy + calcitriol increas ed bone mineral density 3.80% (+/-4.95%) at the femoral neck (P < 0.001), 4 .91% (+/-6.0%) at the spine (P < 0.0001), and parallel changes at the total hip and trochanter. All three treatment groups differed significantly from placebo at the spine and for the hormone replacement therapy/estrogen repl acement therapy groups at the femoral neck, spine, total hip and trochanter . There were no significant differences between combination therapy and hor mone replacement therapy/estrogen replacement therapy alone on bone mineral density at any site in the intent to treat analysis. In a secondary analysis of the effect in women who were adherent to treatme nt, calcitriol had a more significant effect on spine (P = 0.003) and total hip (P = 0.004). The increase in bone mineral density in the adherent grou ps of women was always higher compared with the intent to treat groups. Com bination therapy compared with hormone replacement therapy/estrogen replace ment therapy alone produced a significantly greater response in trochanter (P = 0.007) and total hip bone mineral density (P = 0.0017). In summary, hormone replacement therapy/estrogen replacement therapy alone and in combination with calcitriol therapy was highly effective in reducing bone resorption and increasing bone mineral density at the hip and other c linically relevant sites in a group of elderly women, with normal bone dens ity for their age. Calcitriol was effective in increasing spine bone minera l density. In the adherent women, combination therapy with hormone replacem ent therapy/estrogen replacement therapy and calcitriol increased bone mine ral density significantly more in the total hip and trochanter than did hor mone replacement therapy/estrogen replacement therapy alone.