Preoperative Arterial Embolization for Heterotopic Ossification of the Hip.

PURPOSE: To investigate the efficacy and safety of preoperative arterial embolization for neurogenic heterotopic ossification (NHO) of the hip. MATERIALS AND METHODS: This single-center retrospective study reviewed outcomes in 16 consecutive patients who had surgical resection of NHO of the hip: 8 of whom underwent preoperative arterial embolization and 8 of whom did not. Both patient cohorts had similar baseline characteristics. A mean of 2.62 ± 1.9 arteries per patient, including the gluteal, lateral circumflex femoral, and deep circumflex iliac branches, were embolized using an n-butyl cyanoacrylate (NBCA)-ethiodized oil mixture. Data from both cohorts regarding intraoperative blood loss, volume of blood transfused, complications, and duration of hospitalization were compared. RESULTS: A mean of 2.6 ± 1.9 arteries were embolized with NBCA-ethiodized oil, mainly the gluteal arteries, lateral circumflex femoral artery, and deep circumflex iliac artery. In the embolization group, mean intraoperative blood loss was 875 mL ± 320, mean number of units of blood used was 0.5 ± 0.7, and mean number of days of hospitalization was 6.4 days ± 1.6. In the control group, mean intraoperative blood loss was 1,350 mL ± 120, mean number of units of blood used was 2 ± 1.1, and average number of days of hospitalization was 11.5 days ± 1.4. The embolization group had a mean reduction in blood loss of 40.7% (P = 0.035), reduction in units of blood administered of 75% (P = 0.021), and reduction in days of hospitalization of 44.7% (P = 0.014). No procedural complications were recorded. CONCLUSIONS: Preoperative arterial embolization is effective and safe in reducing intraoperative blood loss, number of hospitalization days, and need for blood transfusions in surgical resection of NHO of the hip.

Heterotopic Ossification Following Arthroplasty for Femoral Neck Fracture.

BACKGROUND: Heterotopic ossification (HO) is a frequent complication following hip surgery. Using data from the Hip Fracture Evaluation with Alternatives of Total Hip Arthroplasty versus Hemiarthroplasty (HEALTH) trial, we aimed to (1) determine the prevalence of HO following total hip arthroplasty (THA) for femoral neck fracture in patients ≥50 years of age, (2) identify whether HO is associated with an increased risk of revision surgery within 24 months after the fracture, and (3) determine the impact of HO on functional outcomes. METHODS: We performed a multivariable Cox regression analysis using revision surgery as the dependent variable and HO as the independent variable. We compared Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores between participants with and those without HO at 24 months. RESULTS: Of 1,441 participants in the study, 287 (19.9%) developed HO within 24 months. HO was not associated with subsequent revision surgery. Grade-III HO was associated with statistically significant and clinically relevant deterioration in the total WOMAC score, which was mainly related to the function component of the score, compared with grade I or II. CONCLUSIONS: The impact of grade-III HO on the functional outcomes and quality of life after THA for hip fracture is clinically important, and HO prophylaxis for selected high-risk patients may be appropriate. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Heterotopic Ossification of the Xiphoid After Chest Compressions.

This report describes the case of a 56-year-old woman with a 6-year history of severe epigastric pain after chest compressions for cardiac arrest. A comprehensive gastrointestinal workup was negative. However, an abdominal computed tomographic scan demonstrated an elongated xiphoid process. After a xiphoid trigger point injection, she experienced pain relief lasting 4 days, and thus her symptoms were attributed to xiphoidalgia secondary to heterotopic ossification after trauma. She underwent open resection of the xiphoid process. Heterotopic ossification of the xiphoid process is rare. This report documents a case of heterotopic ossification secondary to trauma from chest compressions.

Combined use of leptin and mechanical stress has osteogenic effects on ossification of the posterior longitudinal ligament.

PURPOSE: To evaluate the effects of leptin/leptin receptor (LepR) combined with mechanical stress on the development of ossification of the posterior longitudinal ligament (OPLL), which is a disease characterized by ectopic bone formation of the posterior longitudinal ligament (PLL) and can lead to radiculopathy and myelopathy. METHODS: Six human samples of the PLL were analyzed for the expression of leptin and LepR by RT-PCR and western blotting. PLL cells were stimulated with leptin and mechanical stress delivered via a Flexcell tension system, and osteogenic differentiation was evaluated by RT-PCR and western blotting analysis of osteogenic marker expression as well as by alkaline phosphatase (ALP) staining and alizarin red S staining. Activation of mitogen-activated protein kinase (MAPK), Janus kinase (JAK) 2-signal transducer, activator of transcription (STAT) 3 and phosphatidylinositol 3-kinase (PI3K)-Akt was evaluated by western blotting. RESULTS: Samples from the OPLL group had higher LepR mRNA and protein levels and lower leptin levels than those from healthy controls. Exposure to leptin and Flexcell increased the number of ALP-positive cells and calcium nodules in a dose-dependent manner; this effect was accompanied by upregulation of the osteogenic markers osteocalcin, runt-related transcription factor 2 (RUNX2) and osteopontin. Extracellular signal-regulated kinase, P38 MAPK, JAK2, STAT3, PI3K and Akt signaling, was also activated by the combined effects of leptin and mechanical stress. CONCLUSIONS: Leptin and LepR are differentially expressed in OPLL tissues, and the combined use of leptin/LepR and mechanical stress promotes osteogenic differentiation of PLL cells via MAPK, JAK2-STAT3 and PI3K/Akt signaling. These slides can be retrieved under Electronic Supplementary Material.

Palovarotene inhibits connective tissue progenitor cell proliferation in a rat model of combat-related heterotopic ossification.

Heterotopic ossification (HO) develops in the extremities of wounded service members and is common in the setting of high-energy penetrating injuries and blast-related amputations. No safe and effective prophylaxis modality has been identified for this patient population. Palovarotene has been shown to reduce bone formation in traumatic and genetic models of HO. The purpose of this study was to determine the effects of Palovarotene on inflammation, progenitor cell proliferation, and gene expression following a blast-related amputation in a rodent model (n = 72 animals), as well as the ability of Raman spectroscopy to detect early HO before radiographic changes are present. Treatment with Palovarotene was found to dampen the systemic inflammatory response including the cytokines IL-6 (p = 0.01), TNF-α (p = 0.001), and IFN-γ (p = 0.03) as well as the local inflammatory response via a 76% reduction in the cellular infiltration at post-operative day (POD)-7 (p = 0.03). Palovarotene decreased osteogenic connective tissue progenitor (CTP-O) colonies by as much as 98% both in vitro (p = 0.04) and in vivo (p = 0.01). Palovarotene treated animals exhibited significantly decreased expression of osteo- and chondrogenic genes by POD-7, including BMP4 (p = 0.02). Finally, Raman spectroscopy was able to detect differences between the two groups by POD-1 (p < 0.001). These results indicate that Palovarotene inhibits traumatic HO formation through multiple inter-related mechanisms including anti-inflammatory, anti-proliferative, and gene expression modulation. Further, that Raman spectroscopy is able to detect markers of early HO formation before it becomes radiographically evident, which could facilitate earlier diagnosis and treatment. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1135-1144, 2018.

Early local delivery of vancomycin suppresses ectopic bone formation in a rat model of trauma-induced heterotopic ossification.

Heterotopic ossification (HO) is a debilitating sequela of high-energy injuries. It frequently requires surgical excision once symptomatic and there is no practical prophylaxis for combat-injured patients. In this study, we examined the effect of local vancomycin powder on HO formation in a small animal model of blast-related, post-traumatic HO. Male Sprague-Dawley rats were subjected to a polytraumatic extremity injury and amputation with or without methicillin-resistant Staphylococcus aureus infection. Animals were randomized to receive a single local application of vancomycin (20 mg/kg) at the time of injury (POD-0, n = 34) or on postoperative day-3 (POD-3, n = 11). Quantitative volumetric measurement of ectopic bone was calculated at 12-weeks post-injury by micro-CT. Bone marrow and muscle tissues were also collected to determine the bacterial burden. Blood for serum cytokine analysis was collected at baseline and post-injury. Vancomycin treatment on POD-0 suppressed HO formation by 86% and prevented bone marrow and soft tissue infections. We concurrently observed a marked reduction histologically in nonviable tissue, chronic inflammatory cell infiltrates, bone infection, fibrous tissue, and areas of bone necrosis within this same cohort. Delayed treatment was significantly less efficacious. Neither treatment had a marked effect on the production of pro-inflammatory cytokines. Our study demonstrates that local vancomycin treatment at the time of injury significantly reduces HO formation in both the presence and absence of infection, with decreased efficacy if not given early. These findings further support the concept that the therapeutic window for prophylaxis is narrow, highlighting the need to develop early treatment strategies for clinical management. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2397-2406, 2017.

Role of osteoclasts in heterotopic ossification enhanced by fibrodysplasia ossificans progressiva-related activin-like kinase 2 mutation in mice.

Fibrodysplasia ossificans progressiva (FOP) is a disorder of skeletal malformations and progressive heterotopic ossification. The constitutively activating mutation (R206H) of the bone morphogenetic protein type 1 receptor, activin-like kinase 2 (ALK2), is responsible for the pathogenesis of FOP. Although transfection of the causal mutation of FOP into myoblasts enhances osteoclast formation by transforming growth factor-ß (TGF-ß), the role of osteoclasts in heterotopic ossification is unknown. We therefore examined the effects of alendronate, SB431542 and SB203580 on heterotopic ossification induced by the causal mutation of FOP. Total bone mineral content as well as numbers of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated and alkaline phosphatase (ALP)-positive cells in heterotopic bone were significantly higher in muscle tissues implanted with ALK2 (R206H)-transfected mouse myoblastic C2C12 cells than in the tissues implanted with empty vector-transfected cells in nude mice. Alendronate, an aminobisphosphonate, did not affect total mineral content or numbers of TRAP-positive multinucleated and ALP-positive cells in heterotopic bone, which were enhanced by the implantation of ALK2 (R206H)-transfected C2C12 cells, although it significantly decreased serum levels of cross-linked C-telopeptide of type I collagen, a bone resorption index. Moreover, neither SB431542, an inhibitor of TGF-ß receptor type I kinase, nor SB203580, an inhibitor of p38 mitogen-activated protein kinase, affected the increase in heterotopic ossification due to the implantation of ALK2 (R206H)-transfected C2C12 cells. In conclusion, the present study indicates that osteoclast inhibition does not affect heterotopic ossification enhanced by FOP-related mutation.

High LDL levels lead to increased synovial inflammation and accelerated ectopic bone formation during experimental osteoarthritis.

OBJECTIVE: A relation between osteoarthritis (OA) and increased cholesterol levels is apparent. In the present study we investigate OA pathology in apolipoprotein E (ApoE)(-)(/-) mice with and without a cholesterol-rich diet, a model for high systemic low density lipoprotein (LDL) cholesterol levels independent of weight. METHOD: Wild type (WT), Apoe(-)(/-), S100a9(-/-) and Apoe(-)(/-)S100a9(-/-) mice (C57BL/6 background) received a standard or cholesterol-rich diet. Experimental OA was induced by intra-articular injection of collagenase and animals were sacrificed at day 10 and day 36. RESULTS: Although minimal differences in cartilage damage were found between the WT and ApoE(-)(/-) mice, increased synovial thickening was found in the latter. Thirty-six days after OA-induction, ApoE(-)(/-) mice on a standard diet showed increased ectopic bone formation, particularly at the medial collateral ligament, compared with OA in WT mice. Furthermore, a significant increase in synovial gene expression of both S100a8 and S100a9 and S100A8/S100A9 protein levels was found in ApoE(-)(/-) mice, suggesting an activated inflammatory status of synovial cells. In both ApoE(-)(/-) and WT mice, addition of a cholesterol-rich diet resulted in excessive bone formation in the medial collateral ligament at late-time-point OA. Interestingly, at the early time point, proteoglycan deposition was already significantly increased in ApoE(-)(/-) mice compared with WT mice. Mice deficient for both ApoE and S100a9 also showed increased ectopic bone formation, but not synovial activation, suggesting a role for S100-proteins in cholesterol-mediated synovial activation. CONCLUSIONS: Increased cholesterol levels strongly elevate synovial activation and ectopic bone formation in early-stage collagenase-induced OA.

Influence of transcutaneous electrical stimulation on heterotopic ossification: an experimental study in Wistar rats

Heterotopic ossification (HO) is a metaplastic biological process in which there is newly formed bone in soft tissues, resulting in joint mobility deficit and pain. Different treatment modalities have been tried to prevent HO development, but there is no consensus on a therapeutic approach. Since electrical stimulation is a widely used resource in physiotherapy practice to stimulate joint mobility, with analgesic and anti-inflammatory effects, its usefulness for HO treatment was investigated. We aimed to identify the influence of electrical stimulation on induced HO in Wistar rats. Thirty-six male rats (350-390 g) were used, and all animals were anesthetized for blood sampling before HO induction, to quantify the serum alkaline phosphatase. HO induction was performed by bone marrow implantation in both quadriceps of the animals, which were then divided into 3 groups: control (CG), transcutaneous electrical nerve stimulation (TENS) group (TG), and functional electrical stimulation (FES) group (FG) with 12 rats each. All animals were anesthetized and electrically stimulated twice per week, for 35 days from induction day. After this period, another blood sample was collected and quadriceps muscles were bilaterally removed for histological and calcium analysis and the rats were killed. Calcium levels in muscles showed significantly lower results when comparing TG and FG (P<0.001) and between TG and CG (P<0.001). Qualitative histological analyses confirmed 100% HO in FG and CG, while in TG the HO was detected in 54.5% of the animals. The effects of the muscle contractions caused by FES increased HO, while anti-inflammatory effects of TENS reduced HO.

Influence of transcutaneous electrical stimulation on heterotopic ossification: an experimental study in Wistar rats.

Heterotopic ossification (HO) is a metaplastic biological process in which there is newly formed bone in soft tissues, resulting in joint mobility deficit and pain. Different treatment modalities have been tried to prevent HO development, but there is no consensus on a therapeutic approach. Since electrical stimulation is a widely used resource in physiotherapy practice to stimulate joint mobility, with analgesic and anti-inflammatory effects, its usefulness for HO treatment was investigated. We aimed to identify the influence of electrical stimulation on induced HO in Wistar rats. Thirty-six male rats (350-390 g) were used, and all animals were anesthetized for blood sampling before HO induction, to quantify the serum alkaline phosphatase. HO induction was performed by bone marrow implantation in both quadriceps of the animals, which were then divided into 3 groups: control (CG), transcutaneous electrical nerve stimulation (TENS) group (TG), and functional electrical stimulation (FES) group (FG) with 12 rats each. All animals were anesthetized and electrically stimulated twice per week, for 35 days from induction day. After this period, another blood sample was collected and quadriceps muscles were bilaterally removed for histological and calcium analysis and the rats were killed. Calcium levels in muscles showed significantly lower results when comparing TG and FG (P<0.001) and between TG and CG (P<0.001). Qualitative histological analyses confirmed 100% HO in FG and CG, while in TG the HO was detected in 54.5% of the animals. The effects of the muscle contractions caused by FES increased HO, while anti-inflammatory effects of TENS reduced HO.

Isolated Horner Syndrome From an Elongated Styloid Process (Eagle Syndrome).

Eagle syndrome occurs when an elongated styloid process causes otolaryngological or neurological symptoms or signs. We report a patient who had an isolated asymptomatic Horner syndrome that resulted from a pinned internal carotid artery being dynamically injured by an elongated styloid process during chiropractic neck manipulation. There was no evidence of arterial dissection.

Catastrophic stem taper wear in ceramic on polyethylene bearing couple: a case report.

A severe abrasion occurred at the stem taper 13 years after total hip arthroplasty. The bearing couple was 28 mm ceramic on polyethylene. The ceramic head had almost no damage, whereas the stem taper had severe damage. An ectopic bone probably contributed to the abrasion. The ectopic bone had grown to restrict the normal motion in the bearing couple and all stress and torque seemed to concentrate in the junction until the junction obtained mobility instead of the original bearing couple.

Ectopic calcification in diabetic vascular disease.

INTRODUCTION: Cardiovascular diseases represent over one-half of all deaths in both type 1 and type 2 diabetes mellitus. In diabetic patients, vascular calcifications are more frequently observed than in people without diabetes. In particular, elevated degrees of coronary artery and valvular calcifications are reported in populations with diabetes. AREAS COVERED: We will present and discuss findings from clinical and basic science studies that investigate the pathophysiological processes leading to exaggerated arterial/valve calcification in diabetic patients. We will also illustrate the likely effects of the current therapies on vascular calcification progression in diabetic patients. A special focus will be dedicated to the contribution of resident/circulating calcifying cells to the calcific processes observed under diabetic conditions. EXPERT OPINION: Interest in the topic of ectopic calcification in diabetic vascular disease is expanding and more knowledge is adding on its mechanisms and consequences. Importantly, new therapeutic targets are emerging, implying possible future chances to modulate vascular calcification for cardiovascular protection.

Medical rehabilitation of people with spinal cord injury during 40 years of academic physiatric practice.

There are many different paths that lead to an academic physiatric career and a lifelong interest in spinal cord injury (SCI) medicine. It is unfortunate that after decades of cellular-based research in multiple laboratories, there are still no interventions available that can reverse the neurologic loss that follows SCI. In contrast, medical rehabilitation research during the last 40 yrs has led to remarkable improvements in the lives of persons with SCI as evident in their increased life expectancy, shorter hospitalizations, fewer rehospitalizations, and more effective treatments for male sexual dysfunction and fertility, as well as spasticity, heterotrophic ossification, and neuropathic pain. Application of modern technology has improved the mobility of persons with SCI with better designed wheelchairs, decreased their dependency on others, facilitated their access to information, made communication and community integration easier, and so on. Although deaths related to urinary tract complications are now rare, better methods of managing the neurogenic bladder are still needed. Furthermore, better management methods are also needed for the neurogenic bowel, SCI pain, and osteoporosis of the paralyzed limbs. Even with proper prophylaxis, deep vein thrombosis and pulmonary embolism are still common, and clinicians have paid too little attention to reducing the risk for persons with SCI of developing obesity, diabetes mellitus, and cardiovascular disease. These challenges need to be met by medical rehabilitation research, by advocating for insurance policies that support the healthcare needs of persons with SCI, and by developing comprehensive disability policies, all with the support and leadership of academic physiatrists.

Periarticular infiltration in total hip replacement: effect on heterotopic ossification, analgesic requirements and outcome.

BACKGROUND: Up to 80% of patients develop heterotopic ossification (HO) following total hip replacement (THR) and high grades may adversely affect outcome. This study investigated the influence of local infiltration of a NSAID (Ketorolac) and local anaesthetic on the incidence and grade of HO following THR, the effect on post-operative opiate analgesic requirement and on patient reported outcome score. METHODS: A retrospective study was performed on 118 THRs performed without periarticular infiltration from 2003 to 2005, and on 211 performed with infiltration from 2005 to 2008. Pre-operative and 12-month radiographs were examined and HO graded according to the Brooker classification. Peri-operative analgesic requirements and NSAID use were noted and outcome was measured at 1 year with the Oxford Hip Score. RESULTS: Univariate and multivariate analysis indicated that single-dose periarticular NSAID infiltration did not reduce the incidence or grade of HO. Preoperative HO (p = 0.005) and enthesopathy (p = 0.027) were significant predictors of post-operative HO. The use of post-operative oral NSAID (except aspirin) significantly reduced HO (p = 0.001). Periarticular infiltration significantly reduced opiate analgesia use in the first 24 h (p < 0.001) and length of inpatient stay (p < 0.001). There was no difference in Oxford Hip Score at 1 year. CONCLUSION: Preoperative enthesopathies are a risk factor for postoperative HO. Periarticular infiltration of NSAID and local anaesthetic does not reduce HO incidence or grade in THR, but does reduce perioperative opiate requirements and length of hospital stay.

Lipogranuloma with osseous metaplasia in the breast that developed after "Bu-Hwang" oriental medicine treatment.

A lipogranuloma is an inflammatory reactive process associated with exogenous or endogenous lipids, and it's occurrence in the breast has rarely been reported. Osseous metaplasia, which is used to describe bone formation in abnormal locations, can develop from several conditions such as trauma or a tumor. However, few studies have reported benign breast lesions that have been seen as osseous metaplasia. We present a case of a benign calcified breast lesion that developed after a traumatic treatment process called "Bu-Hwang", and it was confirmed as a lipogranuloma with osseous metaplasia. To the best of our knowledge, this is the first reported case of a lipogranuloma with osseous metaplasia in the breast.

Lipogranuloma with Osseous Metaplasia in the Breast That Developed after "Bu-Hwang" Oriental Medicine Treatment

A lipogranuloma is an inflammatory reactive process associated with exogenous or endogenous lipids, and it's occurrence in the breast has rarely been reported. Osseous metaplasia, which is used to describe bone formation in abnormal locations, can develop from several conditions such as trauma or a tumor. However, few studies have reported benign breast lesions that have been seen as osseous metaplasia. We present a case of a benign calcified breast lesion that developed after a traumatic treatment process called "Bu-Hwang", and it was confirmed as a lipogranuloma with osseous metaplasia. To the best of our knowledge, this is the first reported case of a lipogranuloma with osseous metaplasia in the breast.

Pulse low-intensity electromagnetic field as prophylaxis of heterotopic ossification in patients with traumatic spinal cord injury.

BACKGROUND/AIM: Heterotopic ossification (HO) is an important complication of head and spinal cord injuries (SCI). Pulse low-intensity electromagnetic field (PLIMF) therapy increases blood flow to an area of pain or inflammation, bringing more oxygen to that area and helps to remove toxic substances. The aim of this study was to determine the effect of PLIMF as prophylaxis of HO in patients with SCI. METHODS: This prospective random control clinical study included 29 patients with traumatic SCI. The patients were randomly divided into experimental (n=14) and control group (n=15). The patients in the experimental group, besides exercise and range of motion therapy, were treated by PLIMF of the following characteristics: induction of 10 mT, frequency of 25 Hz and duration of 30 min. Pulse low-intensity electromagnetic field therapy started in the 7th week after the injury and lasted 4 weeks. The presence or absence of HO around the patients hips we checked by a plane radiography and Brookers classification. Functional capabilities and motor impairment were checked by Functional Independent Measure (FIM), Barthel index and American Spinal Injury Association (ASIA) impairment class. Statistic analysis included Kolmogorov-Smimrnov test, Shapiro-Wilk test, Mann Whitney Exact test, Exact Wilcoxon signed rank test and Fischer Exact test. Statistical significance was set up to p<0.05. RESULTS: At the end of the treatment no patient from the experimental group had HO. In the control group, five patients (33.3%) had HO. At the end of the treatment the majority of the patients from the experimental group (57.14%) moved from ASIA-A to ASIA-B class. CONCLUSION: Pulse low-intensity electromagnetic field therapy could help as prophylaxis of HO in patients with traumatic SCI.

Heterotopic bone formation around sintered porous-surfaced Ti-6Al-4V implants coated with native bone morphogenetic proteins.

PURPOSE: Coating endosseous dental implants with growth factors such as bone morphogenetic proteins (BMPs) may be one way to accelerate and/or enhance the quality of osseointegration. The purpose of this study was to investigate in the murine muscle pouch model whether sintered porous-surfaced titanium alloy implants coated with BMPs would lead to heterotopic bone formation around and within the implant surface geometry. MATERIALS: Porous-surfaced dental implants were coated with partially purified native human BMPs, with or without a carrier of Poloxamer 407 (BASF Corp., Parsippany, NJ), placed in gelatin capsules and implanted into the hindquarter muscles of mice. Mice were euthanized after 28 days. Sections of retrieved specimens were subsequently prepared for morphometric analysis of bone formation using backscatter electron microscopic images. RESULTS: Human BMPs, either with or without the carrier of Poloxamer 407, led to bone formation within and outside of the sintered porous implant surface. When the sintered implant surface region was subdivided into inner and outer halves, similar levels of bone ingrowth and contact were seen in the 2 halves. Evidence of bone formation to the depth of the solid implant core (i.e., the deepest level possible) also was seen. DISCUSSION AND CONCLUSIONS: Sintered porous-surfaced dental implants can be used as substrate for partially purified BMPs in the murine muscle pouch model. With the addition of these osteoinductive factors, the porous implant surface supported bone formation within the surface porosity provided, in some instances, all the way to the solid implant core. The addition of growth factors to a sintered porous surface may be an efficient method for altering locally the healing sequence and quality of bone associated with osseointegration of bone-interfacing implants.