Aging is associated with a function decline in tissue homeostasis and tissue repair. Aging is also associated with an increased incidence in osteopenia and osteoporosis, but whether these low bone mass diseases are a risk factor for delayed bone healing still remains controversial. Addressing this question is of direct clinical relevance for dental patients, since most implants are performed in older patients who are at risk of developing low bone mass conditions. The objective of this study was to assess how an osteopenic/osteoporotic phenotype affected the rate of new alveolar bone formation. Using an ovariectomized (OVX) rat model, the rates of tooth extraction socket and osteotomy healing were compared with age-matched controls. Imaging, along with molecular, cellular, and histologic analyses, demonstrated that OVX produced an overt osteoporotic phenotype in long bones, but only a subtle phenotype in alveolar bone. Nonetheless, the OVX group demonstrated significantly slower alveolar bone healing in both the extraction socket, and in the osteotomy produced in a healed extraction site. Most notably, osteotomy site preparation created a dramatically wider zone of dying and dead osteocytes in the OVX group, which was coupled with more extensive bone remodeling and a delay in the differentiation of osteoblasts. Collectively, these analyses demonstrate that the emergence of an osteoporotic phenotype delays new alveolar bone formation.
Our long-term objective is to devise methods to improve osteotomy site preparation and, in doing so, facilitate implant osseointegration. As a first step in this process, we developed a standardized oral osteotomy model in ovariectomized rats. There were 2 unique features to this model: first, the rats exhibited an osteopenic phenotype, reminiscent of the bone health that has been reported for the average dental implant patient population. Second, osteotomies were produced in healed tooth extraction sites and therefore represented the placement of most implants in patients. Commercially available drills were then used to produce osteotomies in a patient cohort and in the rat model. Molecular, cellular, and histologic analyses demonstrated a close alignment between the responses of human and rodent alveolar bone to osteotomy site preparation. Most notably in both patients and rats, all drilling tools created a zone of dead and dying osteocytes around the osteotomy. In rat tissues, which could be collected at multiple time points after osteotomy, the fate of the dead alveolar bone was followed. Over the course of a week, osteoclast activity was responsible for resorbing the necrotic bone, which in turn stimulated the deposition of a new bone matrix by osteoblasts. Collectively, these analyses support the use of an ovariectomy surgery rat model to gain insights into the response of human bone to osteotomy site preparation. The data also suggest that reducing the zone of osteocyte death will improve osteotomy site viability, leading to faster new bone formation around implants.
Objectives: Annual completion of a Valproate Risk Acknowledgement Form (RAF) is mandated in the United Kingdom due to neurodevelopmental risks of in utero valproate exposure. The number of women of childbearing potential taking valproate, the uptake of the RAF within this population and their clinical outcomes is not known or monitored. This study surveyed responses of clinicians administering the RAF to women of childbearing potential taking valproate medications. Materials and Methods: Study design-national online survey distributed to clinical specialists throughout the United Kingdom via their national organizations. Participants-clinicians qualified to counsel and administer the valproate RAF (as defined by the Medicines and Healthcare products Regulatory Agency). Main outcome measures-quantitative and qualitative responses regarding identification, uptake, effects and reactions to the RAF. Trial registration-registered at the Clinical Governance and Audit Committee at Royal Free London NHS Foundation Trust Hospital.Results: 215 respondents covering more than 4775 patient encounters were captured. Most patients continued on valproate, 90% with epilepsy as the indication.Respondents reported that seizure control deteriorated when switched to levetiracetam (33%) and lamotrigine (43%), compared to 7% when continuing valproate (P < .001).Conclusions: 33%-43% of clinicians reported seizure control deterioration in women changed to alternatives to valproate. Informed consent requires women considering a change are given this information. Systematic capture of data automated through online RAFs and linked to patient outcomes is needed. There remains little data on valproate given for indications other than epilepsy.
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