The effects of 2-year treatment with the aminobisphosphonate alendronate on bone metabolism, bone histomorphometry, and bone strength in ovariectomized nonhuman primates.

This study examined the effect of 2 yr of treatment with the aminobisphosphonate alendronate (ALN) (0.05 or 0.25 mg/kg i.v. ALN every 2 wk) on estrogen deficiency bone loss and bone strength changes in ovariectomized (OVX) baboons (n = 7 per group) and the ALN mode of action at the tissue level. Biochemical markers of bone turnover increased in OVX animals and were maintained by ALN treatment at non-OVX levels (low dose) or below (high dose). 2 yr of treatment produced no cumulative effects on bone turnover markers. Histomorphometry showed a marked increase in cancellous bone remodeling in OVX animals. Activation frequency increased from 0.48 to 0.86 per yr (L5 vertebra), and the osteoid surfaces from 9 to 13.5% (P < 0.05). No changes were observed in eroded and osteoclast surfaces. ALN treatment decreased activation frequency and indices of bone formation to control levels (low dose) or below (high dose), did not change indices of mineralization, and increased bone mineral density (BMD) in the lumbar vertebrae (L2-L4) by 15% at 0.25 mg/kg (P < 0.05), relative to vehicle-treated animals. The mean strength of cancellous bone (L4) increased by 44% (low ALN dose) and 100% (high dose), compared with vehicle. The strength of individual bones correlated with the square of the L2-L4 BMD (r = 0.91, P < 0.0034). In conclusion, ALN treatment reversed the effects of ovariectomy on cancellous bone turnover and increased bone mass and bone strength in baboons.

Effects of 4-amino-1-hydroxybutylidene bisphosphonate on bone biomechanics in rats.

Bisphosphonates inhibit osteoclast-mediated bone resorption, but their effects on the mechanical behavior of bone remain uncertain. This study investigated the effects of 4-amino-1-hydroxybutylidene bisphosphonate (AHBuBP) on the biomechanical and morphologic properties of bone in ovariectomized rats. Sprague-Dawley rats (four groups, n = 6) were ovariectomized at 3 months of age. From 7 to 13 months, the groups received vehicle or 0.28, 2.8, or 28 micrograms/kg of AHBuBP twice weekly through subcutaneous injection. An additional group of control animals (n = 6) received neither surgery nor drug. We determined the stiffness, yield, and ultimate loads of the femoral midshaft, the sixth lumbar (L6) vertebra, and the femoral neck. Geometric properties of the cortical bone were measured from digitized images of the tibial diaphysis at the level of the synostosis. The area fraction of trabecular bone was determined through the midsagittal plane of the fifth lumbar (L5) vertebra. There were no significant differences in the structural properties of the femoral neck and midshaft, with the exception that the medium-dose group had a greater ultimate load than the vehicle group for the femoral midshaft in bending. Cross-sectional analysis of the tibia did not show significant differences in the inertial properties or area. Ovariectomy caused a significant reduction in the stiffness and ultimate load of L6 and in the area fraction of trabecular bone of L5.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of combined prostaglandin and alendronate treatment on the histomorphometry and biomechanical properties of bone in ovariectomized rats.

Prostaglandin E2 (PGE2) has been shown to stimulate both bone resorption and formation in experimental animals, leading to augmentation of trabecular and cortical bone. The amino bisphosphonate alendronate (ALN) is a potent inhibitor of bone resorption. The objectives of this study were to examine if PGE2 stimulation of bone formation was dependent on bone resorption and if the bone accrued as a result of PGE2 treatment contributed to bone strength. The 48 female Sprague-Dawley rats were assigned to six groups as follows: five groups (8/group) were ovariectomized at the age of 6 months. One group was sacrificed 2 months later to establish baseline conditions, and four groups were treated for 25 days with (1) vehicle, (2) PGE2 at 3 mg/kg/day, (3) ALN sc at 0.8 micrograms/kg/day, and (4) PGE2 + ALN at the respective doses. The sixth group served as nonovariectomized untreated controls. Histomorphometric analysis of 6-10 microns thick tibial sections after in vivo fluorochrome double labeling showed that treatment with PGE2 alone increased endocortical mineral apposition rate and bone formation rate, stimulated production of bone trabeculae in the marrow cavity, and increased cortical porosity. Combined ALN + PGE2 treatment prevented the resorption induced by PGE2 but not the stimulation of bone formation on endocortical and periosteal surfaces and resulted in a significant increase in cortical thickness. Consistent with these observations, the femoral midshaft tested to failure in three-point bending showed a significant increase in strength in the PGE2 + ALN group (181 +/- 15 N) compared to time 0 controls (145 +/- 23 N) or to the ovariectomized vehicle-treated group (141 +/- 28 N).(ABSTRACT TRUNCATED AT 250 WORDS)

Complex reconstruction for the treatment of dorsolateral peritalar subluxation of the foot. Early results after distraction arthrodesis of the calcaneocuboid joint in conjunction with stabilization of, and transfer of the flexor digitorum longus tendon to, the midfoot to treat acquired pes planovalgus in adults.

BACKGROUND: The successful correction of flatfoot in children through lengthening of the lateral column, osteotomy of the medial cuneiform, and advancement of the posterior tibial tendon led to the introduction of similar procedures to treat acquired pes planovalgus secondary to attrition or rupture of the posterior tibial tendon in adults. However, to our knowledge, no study has been published documenting whether these procedures are effective treatment for acquired flatfoot in adults. METHODS: The functional and radiographic results of complex reconstruction of a painful, flexible flatfoot associated with attrition or rupture of the posterior tibial tendon were evaluated in thirty-six patients (forty-one feet) with use of a detailed questionnaire, a comprehensive physical examination, and a review of the radiographs and the medical record. RESULTS: At a mean of thirty-four months (range, twenty-four to fifty months) postoperatively, thirty-six feet (88 percent) were less painful compared with the preoperative status or were pain-free and five of the six parameters that had been used to assess correction of the deformity radiographically had improved significantly (p<0.0001). Eight feet (20 percent) had a non-union at the calcaneocuboid joint, and thirteen feet (32 percent) had anesthesia or paresthesia of the sural nerve. Twenty-nine feet (71 percent) had had additional operations, including removal of hardware from twenty feet; bone-grafting to treat a nonunion at the site of the calcaneocuboid arthrodesis and revision of the internal fixation in four feet; a medial displacement calcaneal osteotomy because of recurrent valgus angulation of the hindfoot in two feet; and a Lapidus procedure because of a hypermobile tarsometatarsal joint with hallux valgus, a triple arthrodesis because of a nonunion at the site of the calcaneocuboid arthrodesis associated with loss of correction, and a dorsiflexion-abduction wedge osteotomy through the site of the calcaneocuboid arthrodesis (which had healed) for alignment of an overcorrected foot in one foot each. The outcomes of the procedures in thirty-five feet (85 percent) were rated by the patients as satisfactory, and thirty-three (92 percent) of the thirty-six patients (thirty-eight [93 percent] of the forty-one feet) stated that they would have the procedure again if the circumstances were similar. CONCLUSIONS: Despite the high prevalence of postoperative complications, most of our patients were satisfied with the result of the procedure after the short duration of follow-up. We believe that the relief of pain and the restoration of function achieved through effective correction of the severe pes planovalgus deformity account for the satisfactory outcomes in our patients.

Effects of supine positioning and fracture post placement on the perineal countertraction force in awake volunteers.

An instrumented traction post was used to determine the magnitude and direction of the countertraction force applied to the perineum of 15 awake volunteers for a series of 12 positions used in fracture surgery and compared with their corresponding neutral position controls. The results demonstrated that adduction of the affected limb and abduction of the contralateral limb applied the greatest force to the perineum with ipsilateral and contralateral placement of the fracture post. These two maneuvers increased the perineal countertraction force 80% above their respective neutral readings. Abduction of the affected limb reduced the traction force by 50% with ipsilateral and contralateral placement of the fracture post. Flexion-abduction-external rotation of the contralateral leg reduced the forces applied to the perineum by 60% when the fracture post was placed contralateral to the affected limb. Contralateral placement of the post decreased the perineal countertraction force 46% below the value for ipsilateral post placement for this maneuver. Internal and external rotation of the affected limb had no effect on the perineal countertraction force for either placement of the post. There was a significant decrease in the perineal forces for the neutral positions after adduction of the affected limb and abduction of the contralateral limb with ipsilateral placement of the post, indicating that the volunteers shifted on the fracture table in response to pain. There was no significant difference in the direction of the countertraction force for the various positions.(ABSTRACT TRUNCATED AT 250 WORDS)

Vertical shear fractures of the medial malleolus: a biomechanical study of five internal fixation techniques.

Fifty embalmed human tibias were osteotomized to create a simulated vertical shear (supination-adduction) fracture of the medial malleolus and were stabilized using one of five internal fixation techniques. In offset axial testing, which simulated supination-adduction loading, the fixation strength of tibias stabilized with either cortical or cancellous lag screws placed perpendicular to the osteotomy was over five times greater than the strength of those treated with an antiglide plate and nearly two and a half times greater than those treated with cancellous lag screws placed oblique to the osteotomy. The tibias stabilized with cancellous lag screws placed perpendicular to the osteotomy exhibited twice the fixation strength of the tibias stabilized with an antiglide plate and distal lag screw. The tibias stabilized with an antiglide plate and distal lag screw and perpendicularly placed cortical or cancellous lag screws demonstrated three times greater resistance to displacement to the applied supination-adduction load than those stabilized with an antiglide plate alone. In offset transverse testing, to simulate loading in external rotation, the mean failure load of the tibias stabilized with cancellous lag screws placed perpendicular to the osteotomy was over two and a half times greater than those stabilized with an antiglide plate and distal lag screw. No significant differences were observed in the resistance to displacement for these tests. These results support the use of lag screws placed perpendicular to the fracture surface for stabilization of vertical shear fractures of the medial malleolus and indicate that the use of an antiglide plate, with or without a distal lag screw, does not offer any advantage over lag screw fixation.

An evaluation of the use of retrospectively acquired preoperative AOFAS clinical rating scores to assess surgical outcome after elective foot and ankle surgery.

The use of retrospectively acquired preoperative AOFAS rating scores in clinical research to assess the outcomes of elective foot and ankle surgery has not been validated. The data obtained utilizing this methodology may misrepresent the results and lead to spurious conclusions. This investigation compared preoperative AOFAS Ankle-Hindfoot scores obtained before and after surgery from patients who had undergone elective surgery to determine if retrospectively acquired scores match those collected prospectively. Only two out of 47 patients (4%) recalled identical AOFAS scores. The mean difference between the preoperative scores (preoperative score obtained after surgery minus preoperative score obtained before surgery) was -5.3 points. Fifteen patients (32%) had preoperative scores that differed by 20 points or more. Kappa statistics found little agreement among the five elements that comprised the two preoperative scores when responses obtained before and after surgery were compared to one another. The results suggest that preoperative clinical rating scores obtained after elective surgery are a poor predictor of the patient's preoperative condition and that studies which employ retrospectively acquired preoperative AOFAS clinical rating scores may overestimate the benefit of surgery.

Surgery of the rheumatoid foot and ankle.

Numerous reconstructive procedures have been used to address the manifestations of rheumatoid arthritis in the foot and ankle. Clinical studies have documented that these procedures relieve pain, however they often sacrifice motion essential to the normal function of the foot. In the forefoot, metatarsophalangeal joint resection arthroplasty shortens the lever arm of the foot, defunctions the toes, and disables the plantar plate and fat pad. Arthrodesis of the ankle and hindfoot alters gait and the effective transmission of weight-bearing stresses through the foot and ankle. These ablative procedures may provoke the deterioration of adjacent joints and may cripple the long-term function of the lower extremity. The introduction of reconstructive procedures designed to preserve motion in joints essential to function and the recognition and treatment of muscle imbalances associated with bone and joint deformities are recent advances in the surgical management of the rheumatoid foot and ankle.

The lateral column lengthening and medial column stabilization procedures.

The results of medial column stabilization, lateral column lengthening, and combined medial and lateral procedures were reviewed in the treatment of adult acquired flatfoot secondary to posterior tibialis tendon insufficiency. All bony procedures were accompanied by transfer of the flexor digitorum longus tendon to the medial cuneiform or stump of the posterior tibialis tendon and tendoachilles lengthening or gastrocnemius recession. Medial column fusion was performed for naviculocuneiform and cuneiform first metatarsal sag; lateral column lengthening was performed for calcaneovalgus deformity with a flat pitch angle; and combined procedures were performed for complex combined deformities. At 1 to 4 year followup of 65 feet, 88% of the feet that had lateral column lengthening, 80% that had medial column stabilization, and 88% of the feet that had medial and lateral procedures had a decrease in pain or were pain free. The lateral talar first metatarsal angle improved by 16 degrees in the patients in the lateral column lengthening group, 20 degrees in the patients in the medial column stabilization group, and 24 degrees in the patients in the combined medial and lateral procedures group. The anteroposterior talonavicular coverage angle improved by 14 degrees in the patients in the lateral column lengthening group, 10 degrees in the patients in the medial column stabilization group, and 14 degrees in the patients in the combined medial and lateral procedures group. These techniques effectively correct deformity without disrupting the essential joints of the hindfoot and midfoot.

Effects of growth-factor-enhanced culture on a chondrocyte-collagen implant for cartilage repair.

The effects of incubation and addition of growth factors to a chondrocyte-seeded collagen implant for cartilage repair were studied. Type I collagen matrices seeded with lapine articular chondrocytes and unseeded controls cultured in the presence and absence of fibroblast growth factor and insulin for 2, 6, and 9 weeks were subjected to biomechanical, biochemical, and histological analysis. Aggregate modulus of elasticity of seeded implants decreased by half at 6 weeks, then rose by a factor of 10 above initial values. Permeability of seeded implants and their controls decreased steadily. Glycosaminoglycan content peaked at 6 weeks, coinciding with the greatest number of chondrocytes and mitotic activity in seeded implants. Chondrocytes remained phenotypically stable and metabolically active; they incorporated glycosaminoglycan into the extracellular matrix, and formed an organized pericellular environment despite the predicted resorption of the collagen matrix. Adding fibroblast growth factor and insulin tripled the rate of cell turnover and doubled the glycosaminoglycan content of seeded implants, but had no effect on their material properties. In vitro incubation for 6 weeks in the presence of fibroblast growth factor and insulin creates a metabolically and mitotically active chondrocyte-collagen composite for implantation into articular cartilage defects.

Development of a novel osteochondral graft for cartilage repair.

This study reports the development of a novel osteochondral graft for cartilage repair. A technique of proteoglycan extraction via timed enzymatic digestion with hyaluronidase and trypsin and subsequent processing with a chloroform-methanol solution to remove cellular debris from a fresh-frozen bovine osteochondral sample is a method described to prepare a stable biological carrier of low immunogenicity. Lyophilization of the carrier followed by rehydration in a suspension of lapine chondrocytes produced a chimeric xenograft that succeeded in vivo in enhancing cartilage repair. In a pilot study, full-thickness articular cartilage defects treated with these xenografts demonstrated improved healing compared to untreated defects or defects treated with unseeded grafts at 2, 6, and 12 weeks postimplantation. The xenograft provoked a mild inflammatory response; however this did not impede the repair process. Further investigation of this novel chimeric xenograft eventually may yield a method of cartilage repair superior to current methods of treatment.

A comparison of abrasion burr arthroplasty and subchondral drilling in the treatment of full-thickness cartilage lesions in the rabbit.

The purpose of this study was to observe the difference in healing of full-thickness articular cartilage defects treated with burr arthroplasty versus subchondral drilling. Cartilage was shaved off the medial femoral condyles of 39 rabbits without penetrating the subchondral plate. In left knees, two 2.0-mm holes were drilled into the condyle until bleeding was obtained. Right knees underwent a burr arthroplasty until punctate bleeding was observed. Animals were sacrificed at 6, 12, and 24 weeks postoperatively. Joint resurfacing and degenerative changes were evaluated grossly and histologically. Degenerative changes in the cartilage surface were observed with both treatments. Rabbits undergoing subchondral drilling had increased fibrocartilaginous healing with time, with a slight increase in degenerative changes. With burr arthroplasty, there was significant decrease in cartilaginous coverage of the exposed surface as well as progressive increase in degenerative changes. Although both techniques were suboptimal, histological evidence at 6 months suggests that subchondral drilling may result in a longer-lived repair than abrasion arthroplasty in the treatment of full-thickness lesions.