Effect of controlled release of platelet-derived growth factor from a porous hydroxyapatite implant on bone ingrowth.

Platelet-derived growth factor (PDGF) is one of several osteogenic factors which affect bone growth and fracture healing. This study examined the potential of hydroxyapatite (HA) rods with interconnected pores of mean diameter 200 microns to be used as a matrix for the release of PDGF to enhance bone ingrowth into the implant. In the initial phase of the study the sustained release of PDGF from the HA rods was characterized in vitro for two different PDGF loadings, 10 and 100 micrograms per implant. The second phase of the study examined bone ingrowth in HA implants placed into the medullary canals of rabbit femora. The specimens were dumb-bell shaped, with a reduced central diameter so that bone growth across a gap could also be determined. Bone ingrowth into HA implants was compared with growth into HA implants loaded with 100 micrograms of PDGF. Pushout measurements were made of average shear strength across the bone-implant interface and backscatter scanning electron microscopy of thick sections was used to quantify the amount of bone ingrowth into the implant. Although greater interfacial shear strength and area of ingrowth were observed, especially across gap sites, in specimens loaded with PDGF, no difference was statistically significant.

High-dose estrogen inhibits bone resorption and stimulates bone formation in the ovariectomized mouse.

In this study, we have investigated estrogen's capacity to regulate bone formation and resorption in the ovariectomized mouse, evaluating the dose and site dependence of estrogen action on bone modeling and remodeling surfaces. To quantitate bone resorption, the skeletons of fifty 8-week-old Swiss-Webster mice were prelabeled with [3H]tetracycline (3H-T) before initiation of treatment protocols. Ovariectomies (OVX) and sham surgeries were performed 3 days after the final 3H-T injection, and the animals were assigned to treatment groups and injected once per week for 4 weeks with one of the following doses of 17 beta-estradiol (E2): sham/oil vehicle (SV), OVX/oil vehicle, OVX/50 micrograms E2, OVX/250 micrograms E2, and OVX/500 micrograms E2. To assess bone formation, fluorochrome labels were administered 9 and 2 days before sacrifice. At the conclusion of the 4 week protocol, the femora and thoracic vertebrae were removed to quantitate the levels of bone resorption based on the skeletal retention of 3H-T. The tibiae were excised for histomorphometric evaluation of the proximal metaphyses and middiaphyses. Indicative of increased bone resorption, vehicle-treated OVX animals had significantly reduced levels of 3H-T in femora and vertebrae compared to SV mice. This result was consistent with histomorphometric data showing a 49% decrease in cancellous bone area of the proximal tibiae in the OVX/oil-treated group. Treatment of OVX animals with 50 micrograms E2 was sufficient to maintain 3H-T levels in vertebrae at SV values, with higher E2 doeses leading to a dose-dependent increase in the retention of 3H-T at this site.(ABSTRACT TRUNCATED AT 250 WORDS)

High-dose gestagens modulate bone resorption and formation and enhance estrogen-induced endosteal bone formation in the ovariectomized mouse.

To determine if gestagens of two separate classes have differing skeletal actions, we studied the effects of pharmacologic doses of norethisterone acetate (NETA), a 19-nortestosterone, and megestrol acetate (MA), a 17 alpha-hydroxyprogesterone, on bone formation and resorption in intact and in ovariectomized mice. In the same set of experiments, we also attempted to determine if these gestagens can alter the skeletal activity of 17 beta-estradiol (E2). Experimentally, the skeletons of 78 female BALB/c mice were prelabeled with [3H]tetracycline (3H-T). The animals were randomized to 13 groups of 6 mice each 3 days after the final 3H-T injection. Ovariectomies (OVX) were performed on 8 groups and sham operations (SO) on 5 groups. To study the skeletal effects of the gestagens, 4 groups each of the OVX and SO mice were treated with controlled-release pellet implants calculated to deliver 80 or 250 micrograms of NETA or MA per day. To study gestagen interactions with E2, 3 groups of OVX mice were treated with either 40 micrograms/day of E2 or 40 micrograms/day of E2 plus 250 micrograms/day of NETA or MA. One group of OVX and one group of SO animals received placebo pellets. Fluorochrome labels were administered 10 and 11 and 3 and 4 days before sacrifice to allow histomorphometric evaluation of bone formation. At the end of the 60 day protocol, tibiae and thoracic vertebrae were removed and processed for quantitating the levels of bone resorption based on the amounts of 3H-T retained in the bones. The femora were fixed and embedded for comparison of diaphyseal bone histomorphometry, and the humeri and lumbar vertebrae were prepared for bone density determinations. Reflecting an increase in bone resorption, 3H-T levels in tibiae and vertebrae were decreased in placebo-treated OVX animals compared to the placebo-treated SO group (p < 0.01). Treatment of both SO and OVX mice with NETA decreased bone resorption in a dose-dependent manner, but MA had no significant effects on vertebral bone resorption and increased bone resorption in the tibiae (p < 0.01). E2 treatment of OVX mice reduced bone resorption, but there were no significant interactions between the E2 and gestagen treatments on resorptive activity. Based on bone histomorphometry of in vivo fluorochrome labels, both gestagens increased periosteal bone formation rates but had no effect on endosteal bone formation (BFRe). In contrast, E2 treatment of the OVX mice stimulated bone formation at the endosteal surface.(ABSTRACT TRUNCATED AT 400 WORDS)