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Intramedullary injury combined with osteoporosis therapeutics regulates targeted local osteogenesis.

ABSTRACT: Bone marrow ablation prompts transient bone formation in nearly the entire medullary cavity before marrow regeneration occurs. Here, we establish a procedure to direct bone formation in a desired particular site within the medullary cavity for support of biomedical devices. Local intramedullary injury was performed in the tibiae of rats and parathyroid hormone (PTH), alendronate, or saline was administered. Newly generated bone in the medulla was assessed by micro-CT and histology. To evaluate the function of newly generated bone, animals received intramedullary injury in tibiae followed by daily PTH. At day-14, implants were placed in the endocortical bone and the bone response to the implants was assessed. The fate of newly generated bone was compared with and without implants. We found that neither intramedullary injury nor medication alone resulted in bone formation. However, when combined, substantial bone was generated locally inside the diaphyseal medulla. Newly formed bone disappeared without implant placement but was retained with implants. Bone was especially retained around and between the implants. This study found that local bone marrow disruption followed by PTH or alendronate generated substantial cancellous bone locally in the diaphyseal medulla. This approach offers promise as a tissue engineering tool in medicine and dentistry.

SUBMITTER: Miyazaki-Asato Y

PROVIDER: S-EPMC7804436 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Intramedullary injury combined with osteoporosis therapeutics regulates targeted local osteogenesis.

Miyazaki-Asato Yoko Y Koi Kiyono K Fujimoto Hiroki H Kakura Kae K Kido Hirofumi H Yanagi Tsukasa T Yamashita Junro J

Scientific reports 20210112 1

Bone marrow ablation prompts transient bone formation in nearly the entire medullary cavity before marrow regeneration occurs. Here, we establish a procedure to direct bone formation in a desired particular site within the medullary cavity for support of biomedical devices. Local intramedullary injury was performed in the tibiae of rats and parathyroid hormone (PTH), alendronate, or saline was administered. Newly generated bone in the medulla was assessed by micro-CT and histology. To evaluate t ...[more]

PMID: 33436871

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Project description:The Intramedullary Skeletal Kinetic Distractor (ISKD) (Orthofix Inc, Lewisville, TX, USA) is an intramedullary device designed for more comfortable limb lengthening than that with external fixators; lengthening is achieved with this nail using rotational oscillation between two telescoping sections. However, the degree to which this device achieves this goal and its complication rate have not been fully documented.We determined (1) the frequency with which distraction was not achieved at the desired rate, (2) whether pain differed between patients with normally and abnormally distracting nails, (3) risk factors for abnormal nails, and (4) other complications.We analyzed 35 lengthening segments (26 femurs, nine tibias) in 19 patients. Mean length achieved was 47 mm. Femoral nails were categorized into four groups according to distraction rate: normal, runaway (unintentionally faster rate [> 1.5 mm/day]), difficult-to-distract (slower rate [< 0.8 mm/day] requiring manual manipulation but not requiring general anesthesia), and nondistracting (slower rate [< 0.8 mm/day] requiring manual manipulation under general anesthesia or reosteotomy). Possible risk factors, including age, BMI, preoperative thigh circumferences, degree of intramedullary overreaming, and length of the thicker portion of the nail within the distal fragment, were compared among groups. VAS pain scores were compared among groups under three conditions: rest, physiotherapy, and distraction motion. Complications were also analyzed. Minimum followup was 15 months (mean, 26 months; range, 15-38 months) after first-stage surgery.Abnormal distraction rate was observed in 21 of 35 segments (60%; 17 femurs, four tibias). VAS pain scores showed no differences among groups during rest or physiotherapy but were higher (p = 0.02) in the problematic nails (7-8 points) versus normal nails (3 points) during distraction. Only mean length of the thicker portion of the nail within the distal fragment differed between normally and abnormally distracting nails (95 mm versus 100 mm; p = 0.03), although this was unlikely to be clinically important. Complications occurred in 10 patients (53%), including five with decreased ankle ROM during distraction, four with delayed bone healing, and one with mechanical device failure during distraction.Rate control was difficult to achieve with the ISKD nail for femoral and tibial lengthenings, complications were relatively common, and among patients in whom rate control was not achieved, pain levels were high. Based on our findings, we believe that surgeons should avoid use of this nail.Level IV, therapeutic study. See Instructions for Authors for a complete description of levels of evidence.

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Intramedullary injury combined with osteoporosis therapeutics regulates targeted local osteogenesis.

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Intramedullary injury combined with osteoporosis therapeutics regulates targeted local osteogenesis.

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