Comparisons of intraosseous graft healing between the doubled flexor tendon graft and the bone–Patellar tendon–Bone graft in anterior cruciate ligament reconstruction

Purpose: The purpose of this study was to compare intraosseous graft healing between the doubled flexor tendon (FT) graft and the bone–patellar tendon–bone (BPTB) graft in anterior cruciate ligament (ACL) reconstruction. Type of Study: Randomized trial. Methods: A biomechanical and histologic study was conducted with 24 adult beagle dogs. Bilateral ACL reconstructions were performed in each animal. Autogenous doubled FT and BPTB grafts were used for the left and right knees, respectively. Each end of the 2 grafts was tethered with a polyester suture to a screw post with a washer. The animals were then allowed unrestricted activities in their cages. Eight animals were killed at 3, 6, and 12 weeks, respectively. Results: Histologically, the FT graft was anchored to the tunnel wall with newly formed collagen fibers resembling Sharpey’s fibers by 12 weeks. These fibers were more abundant in the anterior (ventral) gap than in the posterior (dorsal) gap. In the BPTB graft, the bone plug was anchored with newly formed bone at 3 weeks, although osteocytes in the plug trabeculae were necrotic for 12 weeks. Degeneration of the tendon-bone junction in the plug progressed at 6 weeks. Tensile testing showed that the weakest site was different not only between the 2 grafts but also between the observation periods. In the FT graft, the weakest site was the graft-wall interface at 3 weeks and the intraosseously grafted tendon at 6 weeks. In the BPTB graft, the weakest site was the graft-wall interface at 3 weeks and the proximal site in the bone plug at 6 weeks. The ultimate failure load of the FT graft was significantly inferior (45.8%) to that of the BPTB graft at 3 weeks (P =.021). At 6 weeks, the load of the FT graft was 85% that of the BPTB graft without a significant difference (P =.395). Conclusions: As to the clinical relevance, the fixation device chosen for soft-tissue fixation appears to be more important than comparing it to the BPTB graft, although this has yet to be conclusively proven.Arthroscopy: The Journal of Arthroscopic and Related Surgery, Vol 17, No 5 (May-June), 2001: pp 461–476     

Proprioceptive skills and functional outcome after anterior cruciate ligament reconstruction with a bone–tendon–bone graft

Several studies have shown that patients with anterior cruciate ligament (ACL) reconstruction have an improved proprioceptive function compared to subjects with ACL-deficient knees. The measurement of functional scores and proprioception potentially provides clinicians with more information on the status of the ACL-reconstructed knees. To evaluate proprioception in patients following ACL reconstruction with a bone–tendon–bone (BTB) graft, we used the angle reproduction in the sitting, lying and standing positions and the one-leg hop test. Forty-five patients between 19 and 52 years of age were investigated in a 36-month period after the operation. For functional performance measurement, the International Knee Documentation Committee (IKDC) score was used. Very good and good results were seen in 95% of cases. All patients returned to the same activity level as seen before ACL repair. There was a significant difference in the active angle reproduction test between the ACL-reconstructed knees and normal knees in the active sitting position. Tests with passive angle adjustment in the sitting, lying and active standing positions did not show any differences in proprioceptive skills. Good to very good results in the one-leg hop test we found in 95% of patients. After ACL reconstruction, deficiencies in the active angle reproduction test were very small but, nevertheless, were still observed. Overall, the functional and proprioceptive outcomes demonstrate results to recommend the procedure.

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Résumé  Plusieurs études ont montré que des patients ayant bénéficié d’une reconstruction du ligament croisé antérieur ont été améliorés sur le plan de la fonction proprioceptive surtout si on compare les sujets à des sujets non traités gardant un déficit au niveau du ligament croisé antérieur. La mesure des différents scores, fonction et proprioception, donne un certain nombre d’informations sur ces genoux qui ont été opérés. Nous avons évalué la proprioception de patients opérés par greffes du ligament croisé antérieur par un greffon de type BTB et évalué cette proprioception en position assise, debout, en appui monopodal et après tests de sauts.45 patients entre 19 et 52 ans ont été analysés sur une période de 36 mois après l’intervention chirurgicale. Le score IKDC a également été mesuré. Les résultats ont été considérés comme très bons dans 95% des cas. Les patients ont repris une activité au même niveau que celle qu’ils avaient avant la réparation. Il n’y a pas de différences significatives entre les genoux reconstruits et le genou normal, notamment en ce qui concerne les tests en positions assises. Un très bon résultat des tests de sauts est retrouvé chez 95% des patients. On peut considérer après reconstruction du ligament croisé antérieur, que la récupération fonctionnelle et proprioceptive est excellente et confirme la nécessité de reconstruire les ligaments après rupture.

     

Patellar tendon rupture 3 years after anterior cruciate ligament reconstruction with a central one third bone–patellar tendon–bone graft

Use of the central one third bone–patellar tendon–bone autograft is an accepted technique for anterior cruciate ligament (ACL) reconstruction. Patellar tendon rupture following ACL reconstruction is an acknowledged, although rarely reported, complication of this procedure. Of the limited patellar tendon rupture cases reported in the literature, most are described early in the postoperative period. We present a case of late patellar tendon rupture more than 3 years after uneventful ACL reconstruction in a 32-year-old man.Arthroscopy: The Journal of Arthroscopic and Related Surgery, Vol 17, No 6 (July-August), 2001: pp 648–652     

Enhancement of in vivo supraspinatus tendon–to-bone healing with an alginate-chitin scaffold and rhBMP-2

IntroductionRotator cuff disorders present a high retear rate despite advances in surgical treatment. Tissue engineering could therefore be interesting in order to try to enhance a more biological repair. RhBMP-2 is one of the most osteogenic growth factors and it also induces the formation of collagen type I. However, it has a short half-life and in order to get a more stable release over time it could be integrated in a more slowly degradable carrier, such as an alginate-chitin scaffold. The aim of this study was to investigate the role of the alginate-chitin scaffold alone and in combination with different concentrations of rhBMP-2 when applied on chronic rotator cuff lesions in a rat model.Materials and MethodsWe performed an experimental study with 80 Sprague-Dawley rats, 8 months old, with a chronic rupture of the supraspinatus tendon that was repaired with a modified Mason Allen suture. A scaffold was applied over the suture and 4 groups were obtained; suture (S) only suture, double control (DC) alginate and chitin scaffold, single sample (SS) scaffold of alginate with rhBMP-2 (20 µg rhBMP-2) and chitin, double sample (DS) a scaffold containing alginate with rhBMP-2 and chitin with rhBMP-2 (40 µg rhBMP-2). Macroscopic, histological and biomechanical studies were performed at 4 months after reparation.ResultsThe modified Åström and Rausing's histological scale (the higher the score the worse outcome, 0 points=native tendon) was applied: S got 52 points compared to DC 30 (p = 0,034), SS 22 (p = 0,009) and DS 16 (p = 0,010). Biomechanically the maximum load was highest in DC (63,05 N), followed by DS (61,60 N), SS (52,35 N) and S (51,08), p = 0,025 DS vs S. As to the elastic constant a higher value was obtained in DC (16,65), DS (12,55) and SS (12,20) compared to S (9,33), p = 0,009 DC vs S and 0,034 DS vs S.ConclusionsThe alginate-chitin scaffold seems to promote a more biological response after the reparation of a chronic rotator cuff lesion. Its effect is further enhanced by the addition of rhBMP-2 since the osteotendinous junction is more native-like and has better biomechanical properties.     

Inability of transforming growth factor-β1, combined with a bioabsorbable polymer paste, to promote healing of bone defects in the rat distal femur

The ability of transforming growth factor-β1 (TGF-β1) to promote bone formation suggests that it may have potential as a therapeutic agent in bone defects. However, there still exists a need for an effective method of delivering TGF-β1 to the site of an osseous defect. In the present study, TGF-β1 was embedded in a bioabsorbable polymer paste (a blend of an l-lactide oligomer and a copolymer of ɛ-caprolactone and dl-lactide). The release of TGF-β1 from the polymer paste was examined in vitro with an enzyme-linked immunosorbent assay, which showed sustained release of active TGF-β1 over a 7-day period. Further, the polymer paste was used to fill a bone defect in the rat distal femur. The amount of TGF-β1 per rat was 50 μg, while in a control group we used an identical polymer paste without the growth factor. After a follow-up of 1 week and 3 weeks, the femurs were examined radiographically, histologically, histomorphometrically, microradiographically, and were also used for tetracycline-labeling studies. TGF-β1 did not enhance healing of the bone defect. A combination of growth factors would probably be a more potent osteoinductor than TGF-β1 alone. Received: 14 October 1999     

Osteocyte control of bone remodeling: is sclerostin a key molecular coordinator of the balanced bone resorption–formation cycles?

Osteocytes, entrapped within a newly mineralized bone matrix, possess a unique cellular identity due to a specialized morphology and a molecular signature. These features endow them to serve as a bone response mechanism for mechanical stress in their microenvironment. Sclerostin, a primarily osteocyte product, is widely considered as a mechanotranduction key molecule whose expression is suppressed by mechanical loading, or it is induced by unloading. This review presents a model suggesting that sclerostin is major mediator for integrating mechanical, local, and hormonal signals, sensed by the osteocytes, in controlling the remodeling apparatus. This central role is achieved through interplay between two opposing mechanisms: (1) unloading-induced high sclerostin levels, which antagonize Wnt-canonical-β-catenin signaling in osteocytes and osteoblasts, permitting simultaneously Wnt-noncanonical and/or other pathways in osteocytes and osteoclasts, directed at bone resorption; (2) mechanical loading results in low sclerostin levels, activation of Wnt-canonical signaling, and bone formation. Therefore, adaptive bone remodeling occurring at a distinct bone compartment is orchestrated by altered sclerostin levels, which regulate the expression of the other osteocyte-specific proteins, such as RANKL, OPG, and proteins encoded by “mineralization-related genes” (DMP1, PHEX, and probably FGF23). For example, under specific terms, sclerostin regulates differential RANKL and OPG production, and creates a dynamic RANKL/OPG ratio, leading either to bone formation or resorption. It also controls the expression of PHEX, DMP1, and most likely FGF23, leading to either bone matrix mineralization or its inhibition. Such opposing up- or down-regulation of remodeling phases allows osteocytes to function as an “external unit”, ensuring transition from bone resorption to bone formation. Mini Abstract: The osteocyte network plays a central role in directing bone response either to mechanical loading, or to unloading, leading correspondingly to bone formation or resorption. This review shows a key role of the osteocyte-produced sclerostin as a major mediator of the molecular mechanisms involved in the process of adaptive bone remodeling     

Medial Achilles tendon island flap—a novel technique to treat reruptures and neglected ruptures of the Achilles tendon

Purpose

There is a strong consensus for surgical treatment of reruptures and neglected ruptures of the Achilles tendon. A number of different surgical techniques have been described and several of these methods include extensive surgical exposure to the calf and technically demanding tendon transfers. The overall risk of complications is high and in particular the risk for wound healing problems, which are triggered by an increased tension in the skin when inserting a bulky graft to cover the rupture. In order to reduce the risk for wound healing problems a new, less complicated surgical technique was developed, as described in this study.

Methods

Nine consecutive patients (including six chronic ruptures and three reruptures) with complicating co-morbidities and with a tendon defect between three and eight centimetres were operated upon using the described novel technique. Patient-reported functional outcome was reported after two to eight years.

Results

All tendon defects were successfully repaired. Neither early nor late surgical complications occurred. High patient satisfaction was reported for all patients.

Conclusions

The new surgical technique with a medial Achilles tendon island flap seems to be safe and results in a good patient reported outcome.     

Implant-free press-fit fixation for bone–patellar tendon–bone ACL reconstruction: 10-year results

Objective

The aim of this study is to determine the outcome of anterior cruciate ligament (ACL) reconstruction without foreign material with patellar tendon bone graft in the fixation with bone dowels near the native insertion.

Materials and methods

Between 1998 and 1999, 189 patients were operated with ACL reconstruction with BTB patellar tendon graft. In a prospective study, 148 (78%) (91M, 57F) patients could be seen for a mean follow-up of 10.3 years. All had foreign material-free press-fit and a bottom-to-top (BTT) fixation in 120° knee flexion. All patients were evaluated with detailed history, clinical examinations, radiographic examination with weight bearing which could be compared to the time of surgery in 64 (43%) patients. Laxity testing was performed in Lachman position with the Rolimeter and pivot shift. All patients were graded according to the IKDC and Tegner activity score.

Results

87% of the patients achieved an IKDC score of A/B. The subjective IKDC score was A/B in 94.6% of the subjects. The average side-to-side difference was 1.42 ± 0.88 mm for the Lachman test, 97% of the patients were rated between 0 and 2 mm. The pivot-shift test was negative in 90% and was observed with a glide in 7% of the patients. Radiological joint space narrowing was found in the medial compartment in 8 (12.4%) cases, and laterally in 9 (14.1%) cases. All these patients had partial or total meniscus resections. The patello-femoral joint space was reduced in 21 (23%) cases. The Tegner activity score changed from 6.9 pre-injury to 5.0 at the 10-year follow-up.

Conclusion

The implant-free fixation of the graft with bone dowels and BTT implantation has good and excellent results after 10 years in more than 80% of the patients. Loss of the meniscus is a main factor contributing to osteoarthritis. Advantages of patellar tendon bone press-fit fixation include anatomical positioning and fast bone-to-bone healing, ease for revision surgery and cost effectiveness.     

HDL cholesterol and bone mineral density: is there a genetic link?

Overwhelming evidence has linked cardiovascular disease and osteoporosis, but the shared root cause of these two diseases of the elderly remains unknown. Low levels of high density lipoprotein cholesterol (HDL) and bone mineral density (BMD) are risk factors for cardiovascular disease and osteoporosis respectively. A number of correlation studies have attempted to determine if there is a relationship between serum HDL and BMD but these studies are confounded by a number of variables including age, diet, genetic background, gender and hormonal status. Collectively, these data suggest that there is a relationship between these two phenotypes, but that the nature of this relationship is context specific. Studies in mice plainly demonstrate that genetic loci for BMD and HDL co-map and transgenic mouse models have been used to show that a single gene can affect both serum HDL and BMD. Work completed to date has demonstrated that HDL can interact directly with both osteoblasts and osteoclasts, but no direct evidence links bone back to the regulation of HDL levels. Understanding the genetic relationship between BMD and HDL has huge implications for understanding the clinical relationship between CVD and osteoporosis and for the development of safe treatment options for both diseases.     

The high bone mass phenotype is characterised by a combined cortical and trabecular bone phenotype: Findings from a pQCT case–control study

High bone mass (HBM), detected in 0.2% of DXA scans, is characterised by a mild skeletal dysplasia largely unexplained by known genetic mutations. We conducted the first systematic assessment of the skeletal phenotype in unexplained HBM using pQCT in our unique HBM population identified from screening routine UK NHS DXA scans.pQCT measurements from the mid and distal tibia and radius in 98 HBM cases were compared with (i) 65 family controls (constituting unaffected relatives and spouses), and (ii) 692 general population controls.HBM cases had substantially greater trabecular density at the distal tibia (340 [320, 359] mg/cm³), compared to both family (294 [276, 312]) and population controls (290 [281, 299]) (p < 0.001 for both, adjusted for age, gender, weight, height, alcohol, smoking, malignancy, menopause, steroid and estrogen replacement use). Similar results were obtained at the distal radius. Greater cortical bone mineral density (cBMD) was observed in HBM cases, both at the midtibia and radius (adjusted p < 0.001). Total bone area (TBA) was higher in HBM cases, at the distal and mid tibia and radius (adjusted p < 0.05 versus family controls), suggesting greater periosteal apposition. Cortical thickness was increased at the mid tibia and radius (adjusted p < 0.001), implying reduced endosteal expansion. Together, these changes resulted in greater predicted cortical strength (strength strain index [SSI]) in both tibia and radius (p < 0.001). We then examined relationships with age; tibial cBMD remained constant with increasing age amongst HBM cases (adjusted β ? 0.01 [? 0.02, 0.01], p = 0.41), but declined in family controls (? 0.05 [? 0.03, ? 0.07], p < 0.001) interaction p = 0.002; age-related changes in tibial trabecular BMD, CBA and SSI were also divergent. In contrast, at the radius HBM cases and controls showed parallel age-related declines in cBMD and trabecular BMD.HBM is characterised by increased trabecular BMD and by alterations in cortical bone density and structure, leading to substantial increments in predicted cortical bone strength. In contrast to the radius, neither trabecular nor cortical BMD declined with age in the tibia of HBM cases, suggesting attenuation of age-related bone loss in weight-bearing limbs contributes to the observed bone phenotype.     

Systemic regulation of angiogenesis and matrix degradation in bone regeneration—Distraction osteogenesis compared to rigid fracture healing

Aim of this study was the investigation of systemic biochemical regulation mechanisms of bone regeneration by angiogenic and matrix-degrading enzymes during distraction osteogenesis compared to rigid osteotomy bone healing.Serum samples of 10 otherwise healthy patients with callus distraction for lower limb-lengthening and 10 osteotomy patients undergoing elective axis correction have been collected prospectively in a standardized time schedule before and up to 6 months after the procedure. At the end of the individual investigation period, concentrations of metalloproteinases (MMP-9, -13), tissue inhibitors of metalloproteinases (TIMP-1, TIMP-2) and the angiogenic factors angiogenin and VEGF have been detected by use of commercially available enzyme immunoassays. Results have been compared to our preliminary study on proMMP-1–3.In distraction osteogenesis, significantly elevated serum concentrations compared to baseline could be detected postoperatively for proMMP-1, MMP-9, TIMP-1, angiogenin and VEGF but not for proMMP-2, proMMP-3 or TIMP-2. In patients with rigid osteotomy healing, MMP-9, TIMP-1, TIMP-2, angiogenin and VEGF were significantly increased respectively. Comparison of both patient collectives revealed significantly higher increases of serum proMMP-1, VEGF and TIMP-1 in distraction patients during the lengthening period and significantly higher serum concentrations of TIMP-2 in late fracture healing period in osteotomy patients. Serum levels of MMP-13 were below the lowest standards, and therefore quantitative analysis was not possible. Bone regeneration in distraction osteogenesis and rigid osteotomy healing is accompanied by systemic increase of matrix-degrading and angiogenic factors in a certain time course and quantity. This might reflect biochemical regulation of local bone healing in the circulation. ProMMP-1, VEGF and TIMP-1 seem to be key regulatory factors during distraction osteogenesis.     

Soft bone - hard arteries: a link?

Chronic kidney disease is characterized by mineral and various bone disorders associated with extraosseous and cardiovascular calcifications. Experimental studies and clinical observations in the general population and in chronic kidney disease patients show an inverse relationship between the extent of cardiovascular calcifications and bone mineral density or bone metabolic activity. Arterial calcification and osteoporosis are frequently observed in the same subjects and progress in parallel in postmenopausal women, and associations between histomorphometric indices of bone activity and vascular calcifications were also observed in patients with chronic and end-stage kidney diseases. The biological linkage between vascular calcifications and bone changes is certainly a part of the aging process, but in many studies these bone-vascular associations remained significant after adjustment for age, which suggests an age-independent causal relationship. Based on clinical and experimental evidence showing an association between bone disorders and functional and structural changes of the arterial system the concept of a bone-vascular axis was established complementary to the classical kidney-bone axis. Nevertheless, the factors or mechanisms accounting for these associations are not well understood, and could result from (1) arterial disease responsible for bone abnormalities; (2) action of common dysmetabolic or 'toxic' factors and mechanisms acting on bones and vessels, or (3) direct or indirect influence of bone cells and metabolism on the arterial system. This short review aims to illustrate these possible mechanisms.     

The relation between fracture activity and bone healing with special reference to the early healing phase – A preclinical study

BackgroundFracture healing outcome is to a great extent steered by the mechanical environment. The importance of early phase mechanical fracture stimulation is still controversially discussed, both clinically and scientifically. Furthermore, the role of fracture activity, defined as the number of stimulatory events per time, is particularly for the direct postoperative phase unknown.MethodsTibial defects of seven Swiss mountain sheep were stabilized with a dynamizable bone fixator, which allowed for defined interfragmentary motion by limiting the maximum axial displacement. The fixator was further equipped with a telemetric measuring unit to continuously log all occurring displacement events above a predefined amplitude threshold over an 8-weeks observation period. Callus size was measured over time from X-rays. Ultimate torsional strength of the healed defects was assessed after euthanasia.ResultsOne animal had to be excluded from the experiment due to technical reasons. The remaining six animals exhibited consistently the highest fracture activity in week 1 post-operation with 6′029 displacement events per week for the animal with the lowest activity and 21′866 events per week for the most active animal. Afterwards fracture activity gradually decreased over time. Strong and significant correlations were found for fracture activity in week 1 and 2 with torsional strength of the healed bone (R ≥ 0.881, p ≤ 0.02). No significant correlations were observed at later timepoints. Fracture activity in week 1 and 2 also correlated strongly with the maximum callus area as measured from X-rays (R ≥ 0.846, p ≤ 0.034).ConclusionsThe data demonstrates a positive effect of, within limits, frequent fracture stimulation on bone healing and suggests the importance of the mechanical environment in the direct post-operative healing phase. Clinically, the findings may advocate for the concept of direct post-operative weight bearing. This, however, requires clinical validation and must be considered within the full clinical context including the risk for fixation failure from overloading.     

Triweekly administration of parathyroid hormone (1–34) accelerates bone healing in a rat refractory fracture model

Background

Some reports have shown that intermittent parathyroid hormone (PTH) (1–34) treatment for patients with delayed union or nonunion have led to successful healing. In this study, we investigated whether systemic intermittent administration of PTH (1–34) has a beneficial effect on bone healing in a rat refractory fracture model.

Methods

We created a refractory femoral fracture model in 32 rats with periosteal cauterization that leads to atrophic nonunion at 8 weeks after surgery. Half the rats received subcutaneous intermittent human PTH (1–34) injections at a dosage of 100 μg/kg, thrice a week for 8 weeks. The other half received the vehicle only. At 8 weeks after fracture, radiographic, histological and mechanical assessments were performed.

Results

Radiographic assessments showed that the union rate was significantly higher in the PTH group than in the control group (P?<?0.05). The degree of fracture repair as scored using the Allen grading system in histological assessment was significantly greater in the PTH group than in the control group (P?<?0.05). The ultimate stress and stiffness measurements were significantly greater in the PTH group than in the control group (p?<?0.05).

Conclusions

We demonstrated that triweekly administration of PTH (1–34) increased union rate and accelerated bone healing in a rat refractory fracture model, suggesting that systemic administration of PTH (1–34) could become a novel and useful therapy for accelerating fracture healing in patients at high risk of delayed union or nonunion.