Osteoclast Activated FoxP3+ CD8+ T-Cells Suppress Bone Resorption in vitro

BACKGROUND: Osteoclasts are the body's sole bone resorbing cells. Cytokines produced by pro-inflammatory effector T-cells (T(EFF)) increase bone resorption by osteoclasts. Prolonged exposure to the T(EFF) produced cytokines leads to bone erosion diseases such as osteoporosis and rheumatoid arthritis. The crosstalk between T-cells and osteoclasts has been termed osteoimmunology. We have previously shown that under non-inflammatory conditions, murine osteoclasts can recruit naïve CD8 T-cells and activate these T-cells to induce CD25 and FoxP3 (Tc(REG)). The activation of CD8 T-cells by osteoclasts also induced the cytokines IL-2, IL-6, IL-10 and IFN-γ. Individually, these cytokines can activate or suppress osteoclast resorption. PRINCIPAL FINDINGS: To determine the net effect of Tc(REG) on osteoclast activity we used a number of in vitro assays. We found that Tc(REG) can potently and directly suppress bone resorption by osteoclasts. Tc(REG) could suppress osteoclast differentiation and resorption by mature osteoclasts, but did not affect their survival. Additionally, we showed that Tc(REG) suppress cytoskeletal reorganization in mature osteoclasts. Whereas induction of Tc(REG) by osteoclasts is antigen-dependent, suppression of osteoclasts by Tc(REG) does not require antigen or re-stimulation. We demonstrated that antibody blockade of IL-6, IL-10 or IFN-γ relieved suppression. The suppression did not require direct contact between the Tc(REG) and osteoclasts. SIGNIFICANCE: We have determined that osteoclast-induced Tc(REG) can suppress osteoclast activity, forming a negative feedback system. As the CD8 T-cells are activated in the absence of inflammatory signals, these observations suggest that this regulatory loop may play a role in regulating skeletal homeostasis. Our results provide the first documentation of suppression of osteoclast activity by CD8 regulatory T-cells and thus, extend the purview of osteoimmunology

Gun Barrel View of the Anterior Pelvic Ring for Percutaneous Anterior Column or Superior Pubic Ramus Screw Placement

Background Traditionally, operative fixation of pelvic and acetabular injuries involves complex approaches and significant complications. Accelerated rehabilitation, decreased soft tissue stripping and decreased wound complications are several benefits driving a recent interest in percutaneous fixation. We describe a new fluoroscopic view to guide the placement of screws within the anterior pelvic ring. Methods Twenty retrograde anterior pelvic ring screws were percutaneously placed in ten cadaveric specimens. Arranging a standard C-arm in a position similar to obtaining a lateral hip image, with angles of 54° ± 2° beam to body, 75° ± 5° of reverse cantilever and 14° ± 6° of outlet, a gun barrel view of the anterior pelvic ring is identified. Fluoroscopic images were taken, and the hemipelvi were harvested to examine the dimensions of the anterior pelvic ring and inspected for any cortical or articular perforation. Results The minimum cranial-to-caudal distance in the anterior pelvic ring was 9 mm (range 6.5–12 mm), and the minimum anterior-to-posterior dimension was 9 mm (range 5–15 mm). All but 2 screws were completely confined within the osseous corridors. Identifiable on final fluoroscopic evaluation, one screw perforated the psoas groove and a second perforated the acetabular dome. Overall, 90 % of our screws were accurately and safely placed, upon the first attempt, within the anterior pelvic ring using the described gun barrel view. Conclusion Employing either open reduction, or following a closed or percutaneous reduction, the anterior pelvic ring gun barrel view can reproducibly guide safe placement of anterior pelvic ring screw fixation

Gun Barrel View of the Anterior Pelvic Ring for Percutaneous Anterior Column or Superior Pubic Ramus Screw Placement

Background Traditionally, operative fixation of pelvic and acetabular injuries involves complex approaches and significant complications. Accelerated rehabilitation, decreased soft tissue stripping and decreased wound complications are several benefits driving a recent interest in percutaneous fixation. We describe a new fluoroscopic view to guide the placement of screws within the anterior pelvic ring. Methods Twenty retrograde anterior pelvic ring screws were percutaneously placed in ten cadaveric specimens. Arranging a standard C-arm in a position similar to obtaining a lateral hip image, with angles of 54° ± 2° beam to body, 75° ± 5° of reverse cantilever and 14° ± 6° of outlet, a gun barrel view of the anterior pelvic ring is identified. Fluoroscopic images were taken, and the hemipelvi were harvested to examine the dimensions of the anterior pelvic ring and inspected for any cortical or articular perforation. Results The minimum cranial-to-caudal distance in the anterior pelvic ring was 9 mm (range 6.5–12 mm), and the minimum anterior-to-posterior dimension was 9 mm (range 5–15 mm). All but 2 screws were completely confined within the osseous corridors. Identifiable on final fluoroscopic evaluation, one screw perforated the psoas groove and a second perforated the acetabular dome. Overall, 90 % of our screws were accurately and safely placed, upon the first attempt, within the anterior pelvic ring using the described gun barrel view. Conclusion Employing either open reduction, or following a closed or percutaneous reduction, the anterior pelvic ring gun barrel view can reproducibly guide safe placement of anterior pelvic ring screw fixation

Gun Barrel View of the Anterior Pelvic Ring for Percutaneous Anterior Column or Superior Pubic Ramus Screw Placement

Background Traditionally, operative fixation of pelvic and acetabular injuries involves complex approaches and significant complications. Accelerated rehabilitation, decreased soft tissue stripping and decreased wound complications are several benefits driving a recent interest in percutaneous fixation. We describe a new fluoroscopic view to guide the placement of screws within the anterior pelvic ring. Methods Twenty retrograde anterior pelvic ring screws were percutaneously placed in ten cadaveric specimens. Arranging a standard C-arm in a position similar to obtaining a lateral hip image, with angles of 54° ± 2° beam to body, 75° ± 5° of reverse cantilever and 14° ± 6° of outlet, a gun barrel view of the anterior pelvic ring is identified. Fluoroscopic images were taken, and the hemipelvi were harvested to examine the dimensions of the anterior pelvic ring and inspected for any cortical or articular perforation. Results The minimum cranial-to-caudal distance in the anterior pelvic ring was 9 mm (range 6.5–12 mm), and the minimum anterior-to-posterior dimension was 9 mm (range 5–15 mm). All but 2 screws were completely confined within the osseous corridors. Identifiable on final fluoroscopic evaluation, one screw perforated the psoas groove and a second perforated the acetabular dome. Overall, 90 % of our screws were accurately and safely placed, upon the first attempt, within the anterior pelvic ring using the described gun barrel view. Conclusion Employing either open reduction, or following a closed or percutaneous reduction, the anterior pelvic ring gun barrel view can reproducibly guide safe placement of anterior pelvic ring screw fixation

Proximal Phalanx And Flexor Digitorum Longus Tendon Biomechanics In Flexor To Extensor Tendon Transfer

Background: The flexor to extensor transfer of the flexor digitorum longus (FDL) tendon has been a relatively common operative procedure for the treatment of a flexible hammer toe deformity and chronic metatarsophalangeal (MTP) joint dislocation. A possible complication of using the tunnel technique rather than the tendon splitting technique is iatrogenic fracture through the drilled tunnel site. The purpose of this investigation was to study the FDL tendon and proximal phalanx dimensions in the area of the transfer procedure in order to improve preoperative planning and minimize postoperative complications. Additionally, this study investigated the force necessary to create a fracture in a predrilled proximal phalanx and attempted to elucidate a relationship between that force and the percentage of bone remaining after the drilling process. Methods: The proximal phalanx and FDL tendon of the second, third, and fourth toes from both the right and the left foot of 14 fresh frozen cadavers were dissected, and the digit was amputated at the MTP joint. A total of 84 toes (42 right, 42 left) were obtained from 14 cadavers. The diameter of the FDL tendon was measured, and the circumference and volume were calculated. Fourteen proximal phalanges of either the right or the left foot were then drilled with a 3.5-mm drill, as is often done in a tendon transfer procedure. The 14 nondrilled bones from the contralateral foot were used as matched controls. Radiographs were then taken of the proximal phalanges, and the dimensions of the drill tunnel and remaining bone were calculated. These measurements were used to calculate the volume of the bone, the volume of the drill tunnel, and the percentage of bone remaining after the drilling process. The bones were then tested for load-to-failure using a biomechanical loading apparatus. Results: The average bone and tendon diameter measurements showed a gradual decrease in size from the second to the fourth digits. The bone removed by drilling the tunnel accounted for approximately 20% to 30% of the total volume of bone. Half of the bones fractured with forces between 100 and 200 N, and the majority of bones with a diameter of less than 6 mm fractured with a force of less than 100 N. Conclusions: The average proximal phalanx and FDL tendon size both showed an overall decrease from the second to the fourth digit, albeit not symmetrically. The proximal phalanx diameter appeared to be the most important factor in determining the strength of the structure. Clinical Relevance: Iatrogenic fracture may occur in proximal phalanges with a diameter of bone less than 6 mm, as there may not be adequate bone strength remaining to withstand postoperative forces

Proximal Phalanx And Flexor Digitorum Longus Tendon Biomechanics In Flexor To Extensor Tendon Transfer

Background: The flexor to extensor transfer of the flexor digitorum longus (FDL) tendon has been a relatively common operative procedure for the treatment of a flexible hammer toe deformity and chronic metatarsophalangeal (MTP) joint dislocation. A possible complication of using the tunnel technique rather than the tendon splitting technique is iatrogenic fracture through the drilled tunnel site. The purpose of this investigation was to study the FDL tendon and proximal phalanx dimensions in the area of the transfer procedure in order to improve preoperative planning and minimize postoperative complications. Additionally, this study investigated the force necessary to create a fracture in a predrilled proximal phalanx and attempted to elucidate a relationship between that force and the percentage of bone remaining after the drilling process. Methods: The proximal phalanx and FDL tendon of the second, third, and fourth toes from both the right and the left foot of 14 fresh frozen cadavers were dissected, and the digit was amputated at the MTP joint. A total of 84 toes (42 right, 42 left) were obtained from 14 cadavers. The diameter of the FDL tendon was measured, and the circumference and volume were calculated. Fourteen proximal phalanges of either the right or the left foot were then drilled with a 3.5-mm drill, as is often done in a tendon transfer procedure. The 14 nondrilled bones from the contralateral foot were used as matched controls. Radiographs were then taken of the proximal phalanges, and the dimensions of the drill tunnel and remaining bone were calculated. These measurements were used to calculate the volume of the bone, the volume of the drill tunnel, and the percentage of bone remaining after the drilling process. The bones were then tested for load-to-failure using a biomechanical loading apparatus. Results: The average bone and tendon diameter measurements showed a gradual decrease in size from the second to the fourth digits. The bone removed by drilling the tunnel accounted for approximately 20% to 30% of the total volume of bone. Half of the bones fractured with forces between 100 and 200 N, and the majority of bones with a diameter of less than 6 mm fractured with a force of less than 100 N. Conclusions: The average proximal phalanx and FDL tendon size both showed an overall decrease from the second to the fourth digit, albeit not symmetrically. The proximal phalanx diameter appeared to be the most important factor in determining the strength of the structure. Clinical Relevance: Iatrogenic fracture may occur in proximal phalanges with a diameter of bone less than 6 mm, as there may not be adequate bone strength remaining to withstand postoperative forces

Proximal Phalanx And Flexor Digitorum Longus Tendon Biomechanics In Flexor To Extensor Tendon Transfer

Background: The flexor to extensor transfer of the flexor digitorum longus (FDL) tendon has been a relatively common operative procedure for the treatment of a flexible hammer toe deformity and chronic metatarsophalangeal (MTP) joint dislocation. A possible complication of using the tunnel technique rather than the tendon splitting technique is iatrogenic fracture through the drilled tunnel site. The purpose of this investigation was to study the FDL tendon and proximal phalanx dimensions in the area of the transfer procedure in order to improve preoperative planning and minimize postoperative complications. Additionally, this study investigated the force necessary to create a fracture in a predrilled proximal phalanx and attempted to elucidate a relationship between that force and the percentage of bone remaining after the drilling process. Methods: The proximal phalanx and FDL tendon of the second, third, and fourth toes from both the right and the left foot of 14 fresh frozen cadavers were dissected, and the digit was amputated at the MTP joint. A total of 84 toes (42 right, 42 left) were obtained from 14 cadavers. The diameter of the FDL tendon was measured, and the circumference and volume were calculated. Fourteen proximal phalanges of either the right or the left foot were then drilled with a 3.5-mm drill, as is often done in a tendon transfer procedure. The 14 nondrilled bones from the contralateral foot were used as matched controls. Radiographs were then taken of the proximal phalanges, and the dimensions of the drill tunnel and remaining bone were calculated. These measurements were used to calculate the volume of the bone, the volume of the drill tunnel, and the percentage of bone remaining after the drilling process. The bones were then tested for load-to-failure using a biomechanical loading apparatus. Results: The average bone and tendon diameter measurements showed a gradual decrease in size from the second to the fourth digits. The bone removed by drilling the tunnel accounted for approximately 20% to 30% of the total volume of bone. Half of the bones fractured with forces between 100 and 200 N, and the majority of bones with a diameter of less than 6 mm fractured with a force of less than 100 N. Conclusions: The average proximal phalanx and FDL tendon size both showed an overall decrease from the second to the fourth digit, albeit not symmetrically. The proximal phalanx diameter appeared to be the most important factor in determining the strength of the structure. Clinical Relevance: Iatrogenic fracture may occur in proximal phalanges with a diameter of bone less than 6 mm, as there may not be adequate bone strength remaining to withstand postoperative forces