The combined effect of parathyroid hormone and bone graft on implant fixation.

Impaction allograft is an established method of securing initial stability of an implant in arthroplasty. Subsequent bone integration can be prolonged, and the volume of allograft may not be maintained. Intermittent administration of parathyroid hormone has an anabolic effect on bone and may therefore improve integration of an implant. Using a canine implant model we tested the hypothesis that administration of parathyroid hormone may improve osseointegration of implants surrounded by bone graft. In 20 dogs a cylindrical porous-coated titanium alloy implant was inserted into normal cancellous bone in the proximal humerus and surrounded by a circumferential gap of 2.5 mm. Morsellised allograft was impacted around the implant. Half of the animals were given daily injections of human parathyroid hormone (1-34) 5 µg/kg for four weeks and half received control injections. The two groups were compared by mechanical testing and histomorphometry. We observed a significant increase in new bone formation within the bone graft in the parathyroid hormone group. There were no significant differences in the volume of allograft, bone-implant contact or in the mechanical parameters. These findings suggest that parathyroid hormone improves new bone formation in impacted morsellised allograft around an implant and retains the graft volume without significant resorption. Fixation of the implant was neither improved nor compromised at the final follow-up of four weeks.

The anabolic effect of PTH on bone is attenuated by simultaneous glucocorticoid treatment.

Glucocorticoids (GC) are used for the treatment of a wide spectrum of diseases because of their potent anti-inflammatory and immunosuppressive effects, and they are serious and common causes of secondary osteoporosis. Administration of intermittent parathyroid hormone (PTH) may induce formation of new bone and may counteract the bone loss induced by GC treatment. Effects of simultaneous PTH and GC treatment were investigated on bone biomechanics, static and dynamic histomorphometry, and bone metabolism. Twenty-seven-month-old female rats were divided randomly into the following groups: baseline, vehicle, PTH, GC, and PTH + GC. PTH (1-34) 25 mug/kg and GC (methylprednisolone) 2.5 mg/kg were injected subcutaneously each day for a treatment period of 8 weeks. The rats were labeled with fluorochromes 3 times during the experiment. Bone sections were studied by fluorescence microscopy. The PTH injections resulted in a 5-fold increase in cancellous bone volume. At the proximal tibia, PTH induced a pronounced formation of new cancellous bone which originated from the endocortical bone surfaces and from thin trabeculae. Formation and modeling of connections between trabeculae were observed. Similar but less pronounced structural changes were seen in the PTH + GC group. The compressive strength of the cancellous bone was increased by 6-fold in the PTH group compared with the vehicle group. GC partially inhibited the increase in compressive strength induced by PTH. Concerning cortical bone, PTH induced a pronounced increase in the endocortical bone formation rate (BFR) and a smaller increase in periosteal BFR. The combination of PTH + GC resulted in a partial inhibition of the PTH-induced increase in bone formation. Serum-osteocalcin was increased by 65% in the PTH group and reduced by 39% in the GC group. The pronounced anabolic effect of PTH injections on the endocortical and trabecular bone surfaces and less pronounced anabolic effect on periosteal surfaces were partially inhibited, but not prevented, by simultaneous GC treatment in old rats. Both cortical and cancellous bone possessed full mechanical competence after treatment with PTH + GC.

Osteoprotegerin treatment impairs remodeling and apparent material properties of callus tissue without influencing structural fracture strength.

The influence of osteoprotegerin (OPG) treatment on callus formation, callus tissue structural strength, apparent material properties, and histology of tibia fractures in rats was investigated after 3 weeks and 8 weeks of healing. OPG was given intravenously (10 mg/kg twice weekly) during the entire observation period, and control animals with fractures received vehicle only. When compared with control fractures after 3 weeks of healing, OPG treatment reduced the number of osteoclasts in the callus tissue (93%, P < 0.001) and hampered resorption of genuine cortical bone in the fracture line; OPG treatment did not influence callus dimensions, callus bone mineral content (BMC), fracture structural strength, or callus tissue apparent material properties. When compared with control fractures after 8 weeks of healing; OPG treatment reduced the number of osteoclasts in callus tissue (92%, P < 0.001), augmented callus dimensions (anteriorposterior diameter: 12%, P = 0.034, mediolateral diameter: 13%, P = 0.013), and increased callus BMC (50%, P = 0.007); OPG treatment hampered deposition of new woven bone at the fracture line of the genuine cortical bone (new woven bone present in all vehicle animals, but only in 13% of the OPG-treated animals (P < 0.001)); OPG treatment did not influence structural strength of the fractures, but decreased apparent material properties of the callus tissue (ultimate stress: 51%, P < 0.001; elastic modulus: 42%, P = 0.033). The experiment demonstrates that OPG treatment does not influence the early callus expansion and fracture strength. However, during the subsequent period of remodelling, OPG treatment impairs the normal remodeling and consolidation processes.

Treatment with parathyroid hormone hPTH(1-34), hPTH(1-31), and monocyclic hPTH(1-31) enhances fracture strength and callus amount after withdrawal fracture strength and callus mechanical quality continue to increase.

The influence of intermittent hPTH(1-34)NH2, hPTH(1-31)NH2, and monocyclic [Leu27]cyclo (Glu22-Lys26)hPTH(1-31)NH2 treatment on callus formation, mechanical strength, and callus tissue mechanical quality of tibial fractures in rats was investigated after 8 and 16 weeks of healing. In the 8 weeks of healing animals, the PTH-peptides were injected subcutaneously during the entire observation period (15 nmol/kg/day [hPTH(1-34)NH2: 15 nmol = 60 microg]), and control animals with fractures were given vehicle. In the 16 weeks of healing animals, the PTH-peptides were injected only during the first 8 weeks of healing (15 nmol/kg/day), after which the animals were left untreated during the rest of the healing period. After the first 8 weeks of healing, increased fracture strength and callus volume were seen in the PTH-treated rats (ultimate load 66%, ultimate stiffness 58%, callus volume 28%), and the three peptides were equally effective. No difference in callus tissue mechanical quality was found between PTH and vehicle animals. After 16 weeks of healing, no differences in fracture strength, callus volume, or callus tissue mechanical quality were seen between PTH and vehicle. When comparing PTH-treated animals at 8 and 16 weeks, fracture strength and callus tissue mechanical quality continued to increase after the withdrawal of PTH (ultimate load 23%, ultimate stress 88%, elastic modulus 87%) and external callus volume declined during this period (27%).

Intermittent parathyroid hormone (1-34) enhances mechanical strength and density of new bone after distraction osteogenesis in rats.

Distraction osteogenesis is used both for leg lengthening and for bone transportation in the treatment of fractures and nonunions. The main problem with this method is that the time until full recovery may be up to a year, partly because of the time needed for the new formed bone to consolidate and become strong enough for weight bearing. We have studied whether intermittent parathyroid hormone (PTH(1-34)) could accelerate the consolidation of new formed bone after distraction osteogenesis in rats. Forty-seven, 3-months-old male Sprague-Dawley rats underwent lengthening of the right femur using an external fixator. After a middiaphyseal osteotomy and a 7-day latency period, the callus was distracted during 10 days, with a distraction rate of 0.25 mm twice a day. The consolidation time was either 20 days or 40 days after distraction was completed. A dose of 60 microg of human PTH(1-34)/kg body weight/injection or vehicle was given every second day beginning 30 days before the rats were killed. Both femura of each rat were subjected to mechanical testing and dual-energy X-ray absorptiometry. Blinded histological examination was done for the distracted femura. In the 20 days consolidation experiment, PTH(1-34) increased ultimate load (56%), stiffness (117%), total regenerate callus volume (58%), callus BMC (24%) and histologic bone density (35%) compared to untreated distraction osteogenesis specimens. In the 40 days consolidation experiment, PTH(1-34) increased ultimate load (54%), stiffness (55%), callus BMC (33%) and histologic bone density (23%) compared to untreated distraction osteogenesis specimens. Total regenerate callus volume was unchanged. The contralateral femur also became stronger, stiffer and denser under PTH(1-34) treatment, but to a lesser degree. PTH(1-34) might become useful to shorten the consolidation time after distraction osteogenesis in humans.

Local anabolic effects of growth hormone on intact bone and healing fractures in rats.

The local effects of rat growth hormone (rGH) injected at the surfaces of intact tibial diaphyses and healing tibial diaphysial fractures were investigated in 10-month-old female rats. Intact diaphysial bones: rats were injected daily for 14 days with vehicle, 2 microg rGH, or 20 microg rGH at the surface of the right tibial diaphysis. After 10 days of injection the animals were labeled with calcein. At the rGH-injected location, increased external diaphysial bone dimensions and increased calcein-labeled area were seen, and the responses to rGH were dose dependent. The new bone formed at the periosteal surface was woven bone. At the opposite left tibia, no systemic effect of rGH was found. rGH did not influence body weight changes during the treatment, or muscle mass or serum IGF-I at the end of the treatment. Healing diaphysial fractures: a closed fracture was made in the right tibial diaphysis, and stabilized by medullary nailing. The fractures were tested after 21 days and 98 days of healing. During the first 21 days of healing, all rats were injected daily with either vehicle or 20 microg rGH at the surface of the fracture line. In the 21-day healing rGH group, ultimate load, ultimate stiffness, external callus dimensions, and external callus volume of the fractures were increased. rGH did not affect body weight changes during this healing period or serum IGF-I at the end of the healing period. In the 98-day healing rGH group, ultimate load was still increased compared with the vehicle group, although a ninefold increase took place in the vehicle group between days 21 and 98 of healing. External callus dimensions of the fractures were increased in the rGH group, whereas body weight changes during the healing period were not affected.

Low-intensity, high-frequency vibration appears to prevent the decrease in strength of the femur and tibia associated with ovariectomy of adult rats.

The effect of low-intensity, high-frequency vibration on bone mass, bone strength, and skeletal muscle mass was studied in an adult ovariectomized (OVX) rat model. One-year-old female rats were allocated randomly to the following groups: start control, sham OVX, OVX without vibration, OVX with vibration at 17 Hz (0.5g), OVX with vibration at 30 Hz (1.5g), OVX with vibration at 45 Hz (3.0g). Vibrations were given 30 min/day for 90 days. During vibration each group of rats was placed in a box on top of the vibration motor. The amplitude of the vibration motor was 1.0 mm. The animals were labeled with calcein at day 63 and with tetracycline at day 84. The tibia middiaphysis was studied by mechanical testing and dynamic histomorphometry and the femur distal metaphysis by mechanical compression. OVX without vibration increased the periosteal bone formation rate and increased the medullary cross-sectional area, i.e., increased the endocortical resorption and outward anteromedial and lateral drifts of cortical bone at the tibia middiaphysis. OVX also resulted in a reduced maximum bending stress of the tibia diaphysis and a reduced compressive stress of the femur distal metaphysis. Vibration at the highest intensity, i.e., 45 Hz, of OVX rats induced a further increase in periosteal bone formation rate and inhibited the endocortical resorption seen in OVX rats. Furthermore, vibration at 45 Hz inhibited the decline in maximum bending stress and compressive stress induced by OVX. Neither OVX nor OVX with vibration influenced skeletal muscle mass. In conclusion, the results support the idea of a possible beneficial effect of passive physical loading on the preservation of bone in OVX animals.

The growth hormone secretagogue ipamorelin counteracts glucocorticoid-induced decrease in bone formation of adult rats.

The ability of the growth hormone secretagogue (GHS) Ipamorelin to counteract the catabolic effects of glucocorticoid (GC) on skeletal muscles and bone was investigated in vivo in an adult rat model. Groups of 8-month-old female rats were injected subcutaneously for 3 months with GC (methylprednisolone) 9 mg/kg/day or GHS (Ipamorelin) 100 microg/kg three times daily, or both GC and GHS in combination. The maximum tetanic tension of the calf muscles was determined in vivo in a materials testing machine. The maximum tetanic tension was increased significantly, and the periosteal bone formation rate increased four-fold in animals injected with GC and GHS in combination, compared with the group injected with GC alone. In conclusion, the decrease in muscle strength and bone formation found in GC-injected rats was counteracted by simultaneous administration of the growth hormone secretagogue.

Increases in callus formation and mechanical strength of healing fractures in old rats treated with parathyroid hormone.

We studied the effects of intermittent administration of parathyroid hormone (PTH(1-34)) on callus formation and mechanical strength of tibial fractures in 27-month-old rats after 3 and 8 weeks of healing. 200 microg PTH(1-34)/kg was administered daily during both periods of healing, and control animals with fractures were given vehicle. At 3 weeks, PTH treatment increased maximum load and external callus volume by 160% and 208%; at 8 weeks, by 270% and 135%. It also enhanced callus bone mineral content (BMC) by 190% and 388% (3 and 8 weeks). From week 3 to week 8, callus BMC increased by 60% in the vehicle-injected animals, and by 169% in the PTH-treated animals. In the contralateral intact tibia, PTH treatment increased BMC by 18% and 21% (3 and 8 weeks). No differences in body weight were found between the vehicle-injected and the PTH-treated animals during the experiment. In conclusion, PTH treatment enhances fracture strength, callus volume and callus BMC after 3 and 8 weeks of healing.

The effect of monocyclic and bicyclic analogs of human parathyroid hormone (hPTH)-(1-31)NH2 on bone formation and mechanical strength in ovariectomized rats.

The [Leu27]cyclo(Glu22-Lys26)-hPTH-(1-31)NH2 lactam is a stronger stimulator of adenylyl cyclase activity and a better stimulator of trabecular bone in the ovariectomized (OVX) rat model of osteopenia than hPTH-(1-31)NH2. This enhanced activity is due in large part to the stabilization of the amphiphilic receptor-binding alpha-helix in the Ser17-Gln29 region. The goal of the present study was to determine whether further cyclization could produce a more active hPTH analog. To this end, we compared the relative bioactivities of the bicyclic hPTH analog [Glu17,Leu27]cyclo(Lys13-Glu17,Glu22-Lys26)-hPTH-(1-31)NH2, made by replacing Ser17 with Glu17 and introducing a second lactam linkage between Lys13 and Glu17. The relative EC50 for adenylyl cyclase stimulation by the bicyclic hPTH analog was similar to the EC50 of the monocyclic [Leu27]cyclo(Glu22-Lys26)-hPTH-(1-31)NH2, but the bicyclic analog was still more active than hPTH-(1-31)NH2. As expected from adenylyl cyclase stimulation being responsible for PTH's anabolic action, the bicyclic hPTH analog [Glu17, Leu27]cyclo(Lys13-Glu17, Glu22-Lys26)-hPTH-(1-31)NH2 was able to increase femoral trabecular volume and thickness and mechanical strength in OVX rats, but it was no more effective than [Leu27]cyclo(Glu22-Lys26)-hPTH-(1-31)NH2 when injected once daily in a dose of 0.8 nmol/100 g body weight. Thus, further constraint of the conformation of hPTH-(1-31)NH2 by introducing two lactam link-ages between Lys13-Glu17 and Glu22-Lys26 did not raise the osteogenicity above that of the monocyclic analog.

Growth hormone treatment promotes guided bone regeneration in rat calvarial defects.

This study evaluated the biomechanical strength and bone formation in calvarial critical size bone defects covered with expanded polytetrafluoroethylene (e-PTFE) membranes in rats treated systemically with recombinant human growth hormone (rhGH). A full-thickness bone defect, 5 mm in diameter, was trephined in the central part of each parietal bone in 40 one-year-old female Wistar rats, which were randomly assigned to two groups of 20 animals each. The bone defects were covered with an exocranial and an endocranial e-PTFE membrane. From the day of operation, the rhGH-treated animals were given 2.7 mg rhGH/kg/day and the placebo-injected rats were given isotonic sodium chloride. The animals were killed 28 days after operation. The biomechanical test was performed by a punch out test procedure placing a 3.5-mm diameter steel punch in the centre of the right healed defect. After mechanical testing, the newly formed tissue inside the defect was removed and the dry and ash weights were measured. The left healed defects were used for three-dimensional (3D) reconstruction by means of micro-computer tomography (micro-CT). Ultimate load, ultimate stiffness, and energy absorption at ultimate load were significantly increased in the rhGH-treated group (P < 0.003). Also, tissue dry and ash weights were significantly augmented in the rhGH-treated group (P < 0.001). The 3D reconstruction of newly formed bone showed that there was almost twice as much bone volume present in the rhGH-treated defects compared with the placebo group. The experiment demonstrated that rhGH administration enhances bone deposition and mechanical strength of healing rat calvarial defects, covered with e-PTFE membranes.

The effects of growth hormone on cortical and cancellous bone.

Growth hormone (GH) has profound effects on linear bone growth, bone metabolism and bone mass. The GH receptor is found on the cell surface of osteoblasts and osteoclasts, but not on mature osteocytes. In vitro, GH stimulates proliferation, differentiation and extracellular matrix production in osteoblast-like cell lines. GH also stimulates recruitment and bone resorption activity in osteoclast-like cells. GH promotes autocrine/paracrine insulin-like growth factor 1 (IGF-I) production and endocrine (liver-derived) IGF-I production. Some of the GH-induced effects on bone cells can be blocked by IGF-I antibodies, while others cannot. In animal experiments, GH administration increases bone formation and resorption, and enhances cortical bone mass and mechanical strength. When GH induces linear growth, increased cancellous bone volume is seen, but an unaffected cancellous bone volume is found in the absence of linear growth. Patients with acromegaly have increased bone formation and resorption markers. Bone mass results are conflicting because many acromegalics have hypogonadism, but in acromegalics without hypogonadism, increased bone mineral density (BMD) is seen in predominantly cortical bone, and normal BMD in predominantly cancellous bone. Adult patients with growth hormone deficiency have decreased bone mineral content and BMD. GH therapy rapidly increases bone formation and resorption markers. During the first 6-12 months of therapy, declined or unchanged BMD is found in the femoral neck and lumbar spine. All GH trials with a duration of two years or more show enhanced femoral neck and lumbar spine BMD. In osteoporotic patients, GH treatment quickly increases markers for bone formation and resorption. During the first year of treatment, unchanged or decreased BMD values are found, whereas longer treatment periods report enhanced or unchanged BMD values. However, existing trials comprising relatively few patients and limited treatment periods do not allow final conclusions to be drawn regarding the effects of GH on osteoporosis during long-term treatment.

Statin given perorally to adult rats increases cancellous bone mass and compressive strength.

Recently, it has been shown that statins increased cancellous bone formation and volume in 3-month-old rats and induced a minor decrease in osteoclast number. In the present study, one-year-old female rats were given simvastatin (10 mg/kg) or placebo daily for 3 months by a gastric tube. Specimens, 2.0 mm high, were cut transversely from the 5th lumbar vertebral body. The cancellous bone core diameters within the cortical shell of each specimen were delineated by a micro-CT scanner and then the cancellous bone was compressed in a materials testing machine between an upper and a lower platen with a diameter corresponding to the diameter of the cancellous bone core of each specimen. The cancellous bone volume was determined histomorphometrically on transverse sections. The cancellous bone volume in the simvastatin group (52.7 +/- 1.6%, mean value +/- SEM) was increased by 23% compared with the placebo group (42.8 +/- 1.7%). The compressive stress of the cancellous bone from the simvastatin group (31.8 +/- 2.7 MPa) was increased by 24% compared with the placebo group (24.1 +/- 1.9 MPa). No changes were found in cortical bone mass and strength after the statin treatment. In conclusion, statin given perorally to adult rats increased cancellous bone mass and increased cancellous bone compressive strength. The cancellous bone was found to possess normal biomechanical competence after the statin treatment.

The influence of combined parathyroid hormone and growth hormone treatment on cortical bone in aged ovariectomized rats.

The influence of combined parathyroid hormone (PTH) and growth hormone (GH) treatment on bone formation and mechanical strength was investigated in femoral middiaphysial cortical bone from 20-month-old ovariectomized (OVX) rats. The animals were OVX at 10 months of age, and at 18 months they were treated daily for 56 days with PTH(1-34) alone (60 microg/kg), recombinant human GH (rhGH) alone (2.7 mg/kg), or a combination of PTH(1-34) plus rhGH. Vehicle was given to OVX control rats. All animals were labeled at day 28 (calcein) and at day 49 (tetracycline) of the treatment period. PTH(1-34) alone gave rise to formation of a new zone of bone at the endocortical surface. rhGH alone caused substantial bone deposition at the periosteal surface without influencing the endocortical surface. Combined PTH(1-34) plus rhGH administration enhanced bone deposition at the periosteal surface to the same extent as that of rhGH alone. However, the combined treatment resulted in a more pronounced formation of new bone at the endocortical surface than was induced by PTH(1-34) alone. Both PTH(1-34) alone and rhGH alone increased the mechanical strength of the femoral diaphysis, and further increase in mechanical strength resulted from combined PTH(1-34) plus rhGH treatment. OVX by itself induced the characteristic increase in medullary cavity cross-sectional area and a minor decrease in the mechanical quality of the osseous tissue.

Growth hormone and mild exercise in combination increases markedly muscle mass and tetanic tension in old rats.

OBJECTIVE: A decline of skeletal muscle mass and strength is seen with aging and immobilization. Growth hormone (GH) has been shown to increase muscle mass. In the present study the effects of a combination of mild exercise and GH on skeletal musculature tetanic tension, dry defatted weight (DDW), volume, water, fat and collagen concentrations were investigated in old rats. DESIGN: Recombinant human GH (2.7mg/kg per day) was injected subcutaneously for 73 days in 21-month-old female rats. Exercised rats ran on a treadmill, 8 m/min for 1 h/day. The in vivo maximal tetanic tension of the calf musculature (m. soleus, m. plantaris, m. gastrocnemius together) was analysed in anaesthetized rats by stimulating the ischiadic nerve. RESULTS: The maximal tetanic tension was increased by 23% in GH-injected compared to saline-injected rats. Mild exercise + GH in combination resulted in a further 18% increase in maximal tetanic tension. The mild exercise by itself did not influence the maximal tetanic tension significantly when compared with saline injected rats. The GH administration and/or mild exercise did not change skeletal muscle endurance, measured as tetanic tension during 30s of stimulation. Serum IGF-I concentration was increased twofold in GH-injected rats. CONCLUSION: The increased muscle mass induced by GH + mild exercise was associated with a corresponding increase in maximal tetanic tension. Combination of GH + mild exercise resulted in a substantial further increase of muscle mass and maximal tension compared with GH injections alone in these old rats.

Parathyroid hormone (1-34) increases the density of rat cancellous bone in a bone chamber. A dose-response study.

Intermittent treatment with parathyroid hormone I(PTH) has an anabolic effect on both intact cancellous and cortical bone. Very little is known about the effect of the administration of PTH on the healing of fractures or the incorporation of orthopaedic implants. We have investigated the spontaneous ingrowth of callus and the formation of bone in a titanium chamber implanted at the medioproximal aspect of the tibial metaphysis of the rat. Four groups of ten male rats weighing approximately 350 g were injected with human PTH (1-34) in a dosage of 0, 15, 60 or 240 microg/kg/day, respectively, for 42 days from the day of implantation of the chamber. During the observation period the chamber became only partly filled with callus and bone and no difference in ingrowth distance into the chamber was found between the groups. The cancellous density was increased by 90%, 132% and 173% in the groups given PTH in a dosage of 15, 60 or 240 microg/kg/day, respectively. There was a linear correlation between bone density and the log PTH doses (r 2= 0.6). Our findings suggest that treatment with PTH may have a potential for enhancement of the incorporation of orthopaedic implants as well as a beneficial effect on the healing of fractures when it is given in low dosages.

Strong effect of PTH (1-34) on regenerating bone: a time sequence study in rats.

This study compares the effects of parathyroid hormone (PTH) treatment on new bone formation and normal baseline remodelling in rats. To study new bone formation we used a titanium bone chamber, and to study normal remodelling we used the femur and vertebrae from the same animals. One titanium bone chamber was inserted in the proximal tibia of each of 37 rats. The rats were randomly assigned to daily injections of human PTH (1-34) 60 microg/kg) or vehicle control and killed after 2, 4 or 6 weeks. The total distance of bone growth into the chamber was slightly increased by PTH. Body weight was not affected, and there was only a minor increase in trabecular density of the vertebral and femoral cancellous bone after 6 weeks. The only dramatic effect of PTH was seen in the chambers. In the controls, a marrow cavity formed in the chamber so that the cancellous density decreased from 44% to 24%, and 11% over 2, 4 and 6 weeks. In the PTH-treated animals, a dense network of bone trabeculae was found in the entire bone chamber at all times. The cancellous density increased from 48% to 60%, and 73% at 2, 4 and 6 weeks, respectively. The results suggest that PTH treatment can reduce the development of a resorption cavity. Thus, PTH in this model had a net antiresorptive effect, probably solely because it stimulated osteoblastic activity. Even though osteoclastic activity was present throughout the PTH specimens, it was not sufficient to resorb all newly formed bone. Since PTH seemed to have a greater effect on new bone formation in the chamber than on normal bone remodeling, it might become useful for improving the incorporation of orthopedic implants and stimulating fracture repair.

Strength of colonic anastomoses and skin incisional wounds in old rats - influence by diabetes and growth hormone.

The influence of advanced age on the mechanical strength of colonic anastomoses and skin incisional wounds in diabetic rats was investigated after 0 (suture binding capacity) and after 7 days of healing. Furthermore, the effects of growth hormone (GH) injections to old diabetic rats were investigated. Diabetes in old rats did not influence the strength of colonic anastomoses after 0 and 7 days. However, in these diabetic animals, the strength of skin incisional wounds was reduced by 27% after 7 days of healing (P< 0.01). GH injections administered to old diabetic rats doubled the mortality compared with that of saline-injected old diabetic rats (P< 0.01). GH injections did not influence the strength formation of either colonic anastomoses or skin incisional wounds in old normal rats. In conclusion, the healing of colonic anastomoses in diabetic rats was not compromised by old age, while the strength of skin wounds was decreased.

Effect of experimental diabetes and growth hormone administration on the strength of colonic anastomoses in rats.

The influence of growth hormone (GH; 2 mg/kg/day) administration on the mechanical breaking strength of colonic anastomoses in diabetic rats has been investigated on the day of operation (suture binding capacity) and after 4 and 7 days of healing. In diabetic rats, the suture binding capacity was decreased by 26% in both ultimate load and relative failure energy. After 4 days of healing, no difference was observed between control and diabetic animals. After 7 days, relative failure energy in the diabetic animals was reduced by 33%. GH administration to diabetic animals did not alter strength during the first week of healing. We found an increased circumference (33%) and defatted dry weight (22%) of the colon in diabetic rats. In conclusion, diabetes impairs the suture-binding capacity of the colon in rats, while there is only little influence on healing in the following week. GH administration could not influence the strength of colonic anastomoses in diabetic animals.