Electropolished Titanium Implants with a Mirror-Like Surface Support Osseointegration and Bone Remodelling

This work characterises the ultrastructural composition of the interfacial tissue adjacent to electropolished, commercially pure titanium implants with and without subsequent anodisation, and it investigates whether a smooth electropolished surface can support bone formation in a manner similar to surfaces with a considerably thicker surface oxide layer. Screw-shaped implants were electropolished to remove all topographical remnants of the machining process, resulting in a thin spontaneously formed surface oxide layer and a smooth surface. Half of the implants were subsequently anodically oxidised to develop a thickened surface oxide layer and increased surface roughness. Despite substantial differences in the surface physicochemical properties, the microarchitecture and the composition of the newly formed bone were similar for both implant surfaces after 12 weeks of healing in rabbit tibia. A close spatial relationship was observed between osteocyte canaliculi and both implant surfaces. On the ultrastructural level, the merely electropolished surface showed the various stages of bone formation, for example, matrix deposition and mineralisation, entrapment of osteoblasts within the mineralised matrix, and their morphological transformation into osteocytes. The results demonstrate that titanium implants with a mirror-like surface and a thin, spontaneously formed oxide layer are able to support bone formation and remodelling

Antibiotic prescription in bone augmentation and dental implant procedures : a multi-center study

BACKGROUND: Adherence to antibiotic recommendations and safety aspects of restrictive use are important components when combating antibiotic resistance. The primary aim of this study was to assess the impact of national guidelines on antibiotic prescriptions for bone augmentation procedures among dentists working at three specialized clinics. The secondary aim was to assess the occurrence of postoperative infections. METHODS: Medical charts of 400 patients treated with bone augmentation were reviewed: 200 in the years 2010-2011 and 200 in 2014-2015. The Swedish national recommendations for antibiotic prophylaxis were published in 2012. RESULTS: There was a wide variation in antibiotic regiments prescribed throughout the study. The number of patients treated with antibiotic prophylaxis in a single dose of 2 g amoxicillin, and treated as advocated in the national recommendations, was low and decreasing between the two time periods from 25% (n = 50/200) in 2010-2011 to 18.5% (n = 37/200) in 2014-2015. The number of patients not given any antibiotics either as a prophylactic single dose or during the postoperative phase increased (P < 0.001). The administration of a 3-7-days antibiotic prescription increased significantly from 25.5% in 2010-2011 to 35% in 2014-2015. The postoperative infection rates (4.5% and 6.5%) were without difference between the studied periods. Smoking and omitted antibiotic prophylaxis significantly increased the risk of postoperative infection. Logistic regression analyses showed that patient male gender and suffering from a disease were predictive factors for the clinician to adhere to the guidelines. CONCLUSIONS: After introduction of national recommendations for antibiotic prophylaxis before bone augmentation procedures, the patient group receiving a single preoperative dose decreased while the group not given antibiotic prophylaxis increased. There was no difference in occurrence of postoperative infections between the two time periods. The results indicate a need for educational efforts and strategies for implementation of antibiotic prudence and awareness among surgeons performing bone augmentation procedures

Multimodal and Multiscale Characterization of the Bone‐Bacteria Interface in a Case of Medication‐Related Osteonecrosis of the Jaw

Medication-related osteonecrosis of the jaw (MRONJ) is a known side effect of bisphosphonates (BPs). Although bacterial infection is usually present, the etiology of MRONJ remains unknown. Here we apply a multimodal and multiscale (micro-to-nano) characterization approach to investigate the interface between necrotic bone and bacteria in MRONJ. A non-necrotic bone sample was used as control. Both necrotic and non-necrotic bone samples were collected from the jaw of a female individual affected by MRONJ after using BPs for 23 years. For the first time, resin cast etching was used to expose bacteria at the necrotic site. The bone–bacteria interface was also resolved at the nanoscale by scanning transmission electron microscopy (STEM). Nanosized particulates, likely corresponding to degraded bone mineral, were often noted in close proximity to or enclosed by the bacteria. STEM also revealed that the bone–bacteria interface is composed of a hypermineralized front fading into a highly disordered region, with decreasing content of calcium and phosphorus, as assessed by electron energy loss spectroscopy (EELS). This, combined with the variation in calcium, phosphorus, and carbon across the necrotic bone–bacteria interface evaluated by scanning electron microscopy (SEM)-energy dispersive X-ray spectroscopy (EDX) and the lower mineral-to-matrix ratio measured by micro-Raman spectroscopy in necrotic bone, indicates the absence of a mineralization front in MRONJ. It appears that the bone–bacteria interface originates not only from uncontrolled mineralization but also from the direct action of bacteria degrading the bone matrix.

Micrometer-Sized Magnesium Whitlockite Crystals in Micropetrosis of Bisphosphonate-Exposed Human Alveolar Bone

Osteocytes are contained within spaces called lacunae and play a central role in bone remodelling. Administered frequently to prevent osteoporotic fractures, antiresorptive agents such as bisphosphonates suppress osteocyte apoptosis and may be localized within osteocyte lacunae. Bisphosphonates also reduce osteoclast viability and thereby hinder the repair of damaged tissue. Osteocyte lacunae contribute to toughening mechanisms. Following osteocyte apoptosis, the lacunar space undergoes mineralization, termed “micropetrosis”. Hypermineralized lacunae are believed to increase bone fragility. Using nanoanalytical electron microscopy with complementary spectroscopic and crystallographic experiments, postapoptotic mineralization of osteocyte lacunae in bisphosphonate-exposed human bone was investigated. We report an unprecedented presence of ∼80 nm to ∼3 μm wide, distinctly faceted, magnesium whitlockite [Ca₁₈Mg₂(HPO₄)₂(PO₄)₁₂] crystals and consequently altered local nanomechanical properties. These findings have broad implications on the role of therapeutic agents in driving biomineralization and shed new insights into a possible relationship between bisphosphonate exposure, availability of intracellular magnesium, and pathological calcification inside lacunae

Osteonecrosis of the jaw among patients with cancer treated with denosumab or zoledronic acid: Results of a regulator-mandated cohort postauthorization safety study in Denmark, Norway, and Sweden

BACKGROUND Osteonecrosis of the jaw (ONJ) is an adverse effect of antiresorptive treatment. This study estimated incidence proportions and incidence rates of ONJ in cancer patients with bone metastases from solid tumors treated for the prevention of skeletal-related events in routine clinical practice. METHODS This cohort study in Denmark, Norway, and Sweden in 2011-2018 included 3 treatment cohorts: a denosumab inception cohort (DEIC), a zoledronic acid inception cohort (ZAIC), and a denosumab-switch cohort (DESC). The authors estimated 1- to 5-year incidence proportions and incidence rates of ONJ overall, by cancer site (breast, prostate, or other solid tumor), and by country. ONJ diagnoses were confirmed by adjudication. RESULTS There were 1340 patients in the DEIC, 1352 in the ZAIC, and 408 in the DESC. The median ages of the 3 cohorts were 70, 69, and 70 years, respectively; the proportions of men were 72.6%, 53.8%, and 48.3%, respectively; and the median follow-up was 19.8, 12.9, and 13.3 months, respectively. The 5-year incidence proportions of ONJ were 5.7% (95% confidence interval [CI], 4.4%-7.3%) in the DEIC, 1.4% (95% CI, 0.8%-2.3%) in the ZAIC, and 6.6% (95% CI, 4.2%-10.0%) in the DESC. The corresponding ONJ incidence rates per 100 person-years were 3.0 (95% CI, 2.3-3.7), 1.0 (95% CI, 0.6-1.5), and 4.3 (95% CI, 2.8-6.3). Incidence proportions and incidence rates were highest in patients with prostate cancer and in Denmark. CONCLUSIONS This study provides estimates of the risk of medically confirmed ONJ among patients initiating denosumab or zoledronic acid in routine clinical practice in 3 Scandinavian countries. The results varied by cancer site and by country