Continuous parathyroid hormone and estrogen administration increases vertebral cancellous bone volume and cortical width in the estrogen-deficient rat

Generally, it is believed that intermittent administration of parathyroid h ormone (PTH) has an anabolic effect on the skeleton, whereas continuous adm inistration is catabolic. However, there is evidence that continuous exposu re to PTH may have an anabolic effect, for example, in patients with mild p rimary hyperparathyroidism (PHPT). The possibility of delivering PTH contin uously may have important implications for the treatment of osteoporosis, F urthermore, estrogen treatment may be useful in the medical management of P HPT, Therefore, we examined the skeletal effects of continuous administrati on of PTH, with or without estrogen, in the estrogen-deficient rat with est ablished osteopenia, Forty 7-month-old SD rats were divided into four ovari ectomy (OVX) groups and one: sham-operated group. Eight weeks post-OVX, thr ee groups received subcutaneous implants of Alzet mini pumps loaded with PT H(1-34) (30 mug/kg per day), 17 beta -estradiol (10 mug/kg per day) pellet, or both PTH and 17 beta -estradiol separately for 4 weeks. OVX and sham co ntrol groups were given the mini pumps loaded with vehicle, Two doses of ca lcein (10 mg/kg) were given subcutaneously to all rats 2 days and 8 days be fore death. Histomorphometry was performed on cancellous and cortical bone of the fourth lumbar vertebra, At 3 months, post-OVX rats displayed bone lo ss with high bone turnover. Estrogen reversed OVX-mediated high turnover wi thout restoring cancellous bone volume (BV/TV), PTH infusion further increa sed bone turnover and partially restored BV/TV, However, PTH infusion incre ased cortical porosity. Estrogen inhibited PTH-mediated cancellous bone res orption and substantially increased BV/TV above sham control. The combined treatment was associated with a significant increase in peritrabecular fibr osis and woven bone formation. The combined treatment of PTH infusion and e strogen replacement enhanced cortical width but estrogen did not prevent th e PTH-induced cortical tunneling. We conclude that continuous administratio n of PTH and estrogen increases cortical porosity but has substantial benef icial effects on vertebral cancellous bone volume and cortical width in OVX rats.