Combination of BMP-2-releasing gelatin/ß-TCP sponges with autologous bone marrow for bone regeneration of X-ray-irradiated rabbit ulnar defects.

The objective of this study is to evaluate the feasibility of gelatin sponges incorporating ß-tricalcium phosphate (ß-TCP) granules (gelatin/ß-TCP sponges) to enhance bone regeneration at a segmental ulnar defect of rabbits with X-ray irradiation. After X-ray irradiation of the ulnar bone, segmental critical-sized defects of 20-mm length were created, and bone morphogenetic protein-2 (BMP-2)-releasing gelatin/ß-TCP sponges with or without autologous bone marrow were applied to the defects to evaluate bone regeneration. Both gelatin/ß-TCP sponges containing autologous bone marrow and BMP-2-releasing sponges enhanced bone regeneration at the ulna defect to a significantly greater extent than the empty sponges (control). However, in the X-ray-irradiated bone, the bone regeneration either by autologous bone marrow or BMP-2 was inhibited. When combined with autologous bone marrow, the BMP-2 exhibited significantly high osteoinductivity, irrespective of the X-ray irradiation. The bone mineral content at the ulna defect was similar to that of the intact bone. It is concluded that the combination of bone marrow with the BMP-2-releasing gelatin/ß-TCP sponge is a promising technique to induce bone regeneration at segmental bone defects after X-ray irradiation.

A cross-sectional study of the forearm bone density of long-term users of levonorgestrel-releasing intrauterine system.

BACKGROUND: There are concerns about the effect of hormonal contraceptives on bone mineral density (BMD), but there is currently no information available on the effect of the levonorgestrel-releasing intrauterine system (LNG-IUS) on BMD. The objective of this study was to compare the BMD of LNG-IUS users with that of controls using the TCu380A intrauterine device (IUD). MATERIALS AND METHODS: A cross-sectional study paired 53 women, aged 25-51 years, who had been using the LNG-IUS for 7 years, with 53 IUD users, according to age (+/-1 year) and body mass index (BMI; kg/m2) (+/-1). BMD was evaluated at the midshaft of the ulna and the distal radius of the nondominant forearm using double X-ray absorptiometry. RESULTS: Mean age of women was 34 years. BMI was slightly over 25 in both groups. Estradiol was normal. Mean BMD was 0.469 +/- 0.008 and 0.467 +/- 0.009 and 0.409 +/- 0.009 and 0.411 +/- 0.009 at the midshaft of the ulna and distal radius in LNG-IUS and IUD users, respectively, without significant differences. CONCLUSIONS: Women aged 25-51 years, using the LNG-IUS for 7 years, had a mean BMD similar to that of the control group of TCu380A IUD users.

Effect of transforming growth factor-beta1 on bone regeneration in critical-sized bone defects after irradiation of host tissues.

OBJECTIVE: To determine whether sustained release of transforming growth factor (TGF)-beta1 from a gelatin hydrogel would enhance bone regeneration in critical-sized long-bone defects and overcome inhibitory effects of preoperative irradiation. ANIMALS: 24 adult New Zealand White rabbits. PROCEDURE: Rabbits were allocated to 2 groups. Twelve rabbits received localized megavoltage radiation to the right ulna by use of a cobalt 60 teletherapy unit, and 12 rabbits received no irradiation. Then, a 1.5-cm defect was aseptically created in the right ulna of each rabbit. Gelatin hydrogel that contained 5 microg of adsorbed recombinant-human (rh)TGF-beta1 was placed in the defect of 12 rabbits (6 irradiated and 6 nonirradiated), and the other 12 rabbits received hydrogel without rhTGF-beta1. Rabbits were euthanatized 10 weeks after surgery. New bone formation within the defect was analyzed by use of nondecalcified histomorphometric methods. A 1-way ANOVA was used to compare differences among groups. RESULTS: New bone formation within the defect was significantly greater in TGF-beta1-treated rabbits than in rabbits treated with hydrogel carrier alone. Local delivery of rhTGF-beta1 via a hydrogel carrier in irradiated defects resulted in amounts of bone formation similar to those for nonirradiated defects treated by use of rhTGF-beta1. CONCLUSIONS AND CLINICAL RELEVANCE: Local delivery of TGF-beta1 by use of a hydrogel carrier appears to have therapeutic potential for enhancing bone formation in animals after radiation treatments. IMPACT FOR HUMAN MEDICINE: This technique may be of value for treating human patients at risk for delayed bone healing because of prior radiation therapy.

The effect of host tissue irradiation on large-segment allograft incorporation.

Therapeutic radiation delivered to bone and the adjacent local tissues before allograft limb-salvage surgery has been associated with poor graft incorporation and higher numbers of clinical complications. Our objective was to determine the effect of preoperative radiation therapy on specific histologic, molecular and structural parameters of large-segment, bone allograft incorporation in a canine model. Skeletally mature dogs received a total of 0, 25, or 50 Gy of radiation to the foreleg (radius and ulna) delivered in 2-Gy fractions during a 5-week period before reconstruction of a 3.5-cm defect in the radius. The dogs were sacrificed at postoperative day 150. Nondestructive four-point bending was done on the harvested allograft-host bone immediately after euthanasia and specimens were compared using biomechanical, histomorphometric, immunohistochemical, and in situ reverse transcription polymerase chain reaction techniques. Preoperative irradiation significantly impaired allograft incorporation as determined by radiographic healing scores, histomorphometry, and frequency of nonunions. Biochemical differences included diminished bone morphogenetic protein-2 and bone morphogenetic protein-4 protein levels and messenger ribonucleic acid expression. Vascular endothelial growth factor expression was not altered. These data suggest that bone morphogenetic protein-2 and bone morphogenetic protein-4 signaling at the allograft-host junction is altered after preoperative fractionated radiation and provides a plausible albeit partial mechanistic explanation for radiation-mediated delays in allograft incorporation.

Enhancement of bone growth into porous intramedullary implants using non-invasive low intensity ultrasound.

An in vivo study was designed to determine if non-invasive low intensity ultrasound could enhance bone growth into porous intramedullary implants. Fully porous intramedullary rods were implanted bilaterally into the ulnae of six dogs. In each dog, one ulna served as a control and the other was treated with 20 min of daily ultrasound stimulation for 6 consecutive weeks. Analysis of serial transverse sections indicated an average of 119% more bone growth into the ultrasound-treated implants compared with the contralateral controls (P < 0.001). In each of the 6 dogs, there was a significantly greater amount of bone ingrowth on the ultrasound-stimulated side. These data indicate a clear potential for externally applied ultrasound therapy to augment biological fixation.

Microdistribution of 239Pu in the beagle skeleton.

The microdistribution of 239Pu was analyzed in the humerus, lumbar vertebra, and proximal ulna of young adult beagles using neutron induced autoradiography. The animals were sacrificed serially in groups of three at 4, 8, 16, 32, and 64 wk after a single injection of 3.5 kBq kg(-1) body weight. The kinetic behavior of surface concentrations was modeled using a simple concept of deposition and clearance in skeletal regions. Bones with high turnover showed a larger initial uptake and a faster clearance than bones with low turnover rates. Using a regression procedure, the surface deposition and clearance of plutonium was calculated as a function of the turnover rate. With time after injection the initial nonuniformity of trabecular surface labels tends to become more uniform. The trabecular:cortical affinity ratio is about 10. Trabecular activity is gradually translocated to cortical sites. The affinity ratio of forming to resting surfaces is about three. In some bones a continuous increase of marrow stars was observed, whereas in other bones no clear-cut tendency could be seen. The highest level of marrow labeling occurred in the lumbar vertebra and the humerus shaft.

Prevention of heterotopic bone formation with low dose radiation therapy.

Radiation therapy to control heterotopic bone formation does not appear to be commonly used in sites other than hips where effective control is evident following arthroplasty. Reported are the results in 12 sites in 10 patients including three with treatment to the elbow, humerus, and ulna. Ten sites received a radiation dose of 10.00 Gy, one 16.00 Gy, and one was treated to 20.00 Gy, all delivered in 2.00 Gy fractions. Preoperative and follow-up x-rays were reviewed and graded. There was no clinically significant regrowth of heterotopic bone. Five sites (42%) demonstrated mild regrowth or persistence following surgery with the other seven (58%) showing no evidence of heterotopic bone. No complications were seen. Radiation therapy is effective for the prevention of heterotopic bone after total hip arthroplasties as well as surgery for fractures to other areas.

Radiation osteitis: a problem of recognition.

Localized changes of radiation necrosis in 6 patients treated for Ewing sarcoma are described. Well-circumscribed lytic areas in the cortex of a previously irradiated long bone may be mistaken for tumor recurrence, especially if they are few in number and surrounded by relatively normal bone. The clarity of demarcation of these lesions, their progression, and the lack of a periosteal reaction are stressed.

The effect of whole-body irradiation on skeletal growth in rhesus monkeys.

Late effects of single whole-body doses of 400--500 and 750--900 rads on skeletal growth in 32 rhesus monkeys were studied. Findings indicated growth inhibition strongly related to dose and age at irradiation. Doses of 750--900 rads before the age of 40 months resulted in significantly greater growth inhibition (11%) than doses given during or shortly after adolescence (p less than 0.005). Doses of less than 750 rads were not significant. In view of the close similarity between monkeys and man, irradiation of children at doses greater than 750 rads may carry a strong risk of subsequent growth retardation.