L. Susan Taichman

Human Very Small Embryonic-Like Cells Generate Skeletal Structures, In Vivo

Human very small embryonic-like (hVSEL) cells are a resident population of multipotent stem cells in the bone marrow involved in the turnover and regeneration of tissues. The levels of VSEL cells in blood are greatly increased in response to injury, and they have been shown to repair injured tissues. Adult hVSEL cells, SSEA-4(+)/CD133(+)/CXCR4(+)/Lin(-)/CD45(-), express the pluripotency markers (Oct-4 and Nanog) and may be able to differentiate into cells from all 3 germ lineages. hVSEL cells isolated from blood by apheresis following granulocyte-colony-stimulating factor mobilization were fractionated and enriched by elutriation and fluorescence activated cell sorting. Collagen sponge scaffolds containing 2,000-30,000 hVSEL cells were implanted into cranial defects generated in SCID mice. Analysis by microcomputed tomography showed that a cell population containing VSEL cells produced mineralized tissue within the cranial defects compared with controls at 3 months. Histologic studies showed significant bone formation and cellular organization within the defects compared with cellular or scaffold controls alone. Antibodies to human leukocyte antigens demonstrated that the newly generated tissues were of human origin. Moreover, human osteocalcin was identified circulating in the peripheral blood. There was evidence that some level of hVSEL cells migrated away from the defect site, using quantitative real-time polymerase chain reaction to detect for human-specific Alu sequences. This study demonstrates that hVSEL cells are able to generate human bone tissue in a mouse model of skeletal repair. These studies lay the foundation for future cell-based regenerative therapies for osseous and connective tissue disorders, including trauma and degenerative conditions, such as osteoporosis, fracture repair, and neoplastic repair.

Periodontal Health in Women With Early-Stage Postmenopausal Breast Cancer Newly on Aromatase Inhibitors: A Pilot Study

BACKGROUND Aromatase inhibitor (AI) use results in low estrogen levels, which in turn affect bone mineral density (BMD). Periodontitis, alveolar bone loss, and tooth loss are associated with low BMD. The goal of this study is to assess the prevalence of periodontitis and perceived oral health and evaluate salivary biomarkers in postmenopausal women who are survivors of early-stage (I to IIIA) breast cancer (BCa) and receive adjuvant AI therapy. METHODS Participants included 58 postmenopausal women: 29 with BCa on AIs and 29 controls without BCa diagnoses. Baseline periodontal status was assessed with: 1) periodontal probing depth (PD); 2) bleeding on probing (BOP); and 3) attachment loss (AL). Demographic and dental utilization information was gathered by questionnaire. Linear regression modeling was used to analyze the outcomes. RESULTS No differences were found in mean PD or number of teeth. The AI group had significantly more sites with BOP (27.8 versus 16.7; P = 0.02), higher worst-site AL (5.2 versus 4.0 mm; P <0.01), and more sites with dental calculus (18.2 versus 6.4; P <0.001) than controls. Linear regression adjusted for income, tobacco use, dental insurance, and previous radiation and chemotherapy exposure demonstrated that AI use increased AL by >2 mm (95% confidence interval, 0.46 to 3.92). Median salivary osteocalcin and tumor necrosis factor-α levels were significantly higher in the AI group than the control group. CONCLUSION This first investigation of the periodontal status of women initiating adjuvant AI therapy identifies this population as having an increased risk for periodontitis.

Potential implications of adjuvant endocrine therapy for the oral health of postmenopausal women with breast cancer

Current adjuvant treatment modalities for breast cancer that express the estrogen receptor or progesterone receptor include adjuvant anti-estrogen therapies, and tamoxifen and aromatase inhibitors. Bone, including the jaw, is an endocrine-sensitive organ, as are other oral structures. This review examines the potential links between adjuvant anti-estrogen treatments in postmenopausal women with hormone receptor positive breast cancer and oral health. A search of PubMed, EMBASE, CENTRAL, and the Web of Knowledge was conducted using combinations of key terms “breast,” “cancer,” “neoplasm,” “Tamoxifen,” “Aromatase Inhibitor,” “chemotherapy,” “hormone therapy,” “alveolar bone loss,” “postmenopausal bone loss,” “estrogen,” “SERM,” “hormone replacement therapy,” and “quality of life.” We selected articles published in peer-reviewed journals in the English. The authors found no studies reporting on periodontal diseases, alveolar bone loss, oral health, or oral health-related quality of life in association with anti-estrogen breast cancer treatments in postmenopausal women. Periodontal diseases, alveolar bone density, tooth loss, and conditions of the soft tissues of the mouth have all been associated with menopausal status supporting the hypothesis that the soft tissues and bone of the oral cavity could be negatively affected by anti-estrogen therapy. As a conclusion, the impact of adjuvant endocrine breast cancer therapy on the oral health of postmenopausal women is undefined. The structures of the oral cavity are influenced by estrogen; therefore, anti-estrogen therapies may carry the risk of oral toxicities. Oral health care for breast cancer patients is an important but understudied aspect of cancer survivorship.

Depot Medroxyprogesterone Acetate Use and Periodontal Health in 15- to 44-Year-Old US Females

BACKGROUND It has been suggested that progestins may have an inflammatory component and/or increase in prostaglandin synthesis. Thus, extended progestin use may be associated with higher risk of periodontal diseases. This study investigates the association between depot medroxyprogesterone acetate (DMPA) injectable contraception and the prevalence of periodontal diseases among US premenopausal females. METHODS Data for this cross-sectional analysis comes from the 1999 to 2004 National Health and Nutrition Examination Surveys. This analysis includes 4,460 US females (15 to 44 years of age) with complete DMPA usage and periodontal status data. RESULTS Current and past DMPA use was 4.1% and 12.0%, respectively. The prevalence of gingivitis was 53.9% for females who reported having used DMPA compared with 46.1% for DMPA never-users. Females taking DMPA were more likely to be young, single, and non-white, have a history of smoking, have lower levels of education and income, and have ≥1 live births and were less likely to visit the dentist. Using logistic regression, DMPA use was associated with an increased risk of gingivitis (odds ratio [OR] =1.7; 95% confidence interval [CI] = 1.09 to 1.67) and periodontitis (DMPA, OR = 1.49; 95% CI = 1.01 to 2.22) after adjusting for age, race, education, poverty income ratio, dental care use, and smoking status. A significant interaction between smoking status and DMPA use was also found (P = 0.029). CONCLUSIONS This study suggests that DMPA use may be associated with periodontal diseases. Additional investigation is warranted as a result of the disproportionate usage of DMPA among low-income populations who are at an increased risk for poor dental health.

Periodontal health, perceived oral health, and dental care utilization of breast cancer survivors

OBJECTIVES This population-based analysis examined the prevalence of periodontal diseases along with the self-perceived oral health and patterns of dental care utilization of breast cancer survivors in the United States. METHODS Data from the 1999-2004 National Health and Nutrition Surveys were utilized, examining information from 3,354 women between 50 and 85 years of age. Primary outcomes were gingivitis and periodontitis, self-perceived oral health, and dental care utilization. Logistic regression analyses were used to estimate relationships of breast cancer diagnosis and primary outcomes while controlling for confounding factors. RESULTS Breast cancer survivors were more likely to be older than 55 years, white, nonsmokers, have higher levels of education and income, and a higher prevalence of osteoporosis. Breast cancer survivors were significantly less likely to have dental insurance (P = 0.04). Utilization of dental services and reason for last dental visit did not significantly differ between groups. A history of a breast cancer diagnosis did not increase the odds of gingivitis [odds ratio (OR):  1.32; 95 percent confidence interval (CI): 0.53-3.63], periodontitis (OR: 1.82; 95 percent CI:  0.89-4.01), or poor self-perceived oral health (OR: 0.89; 95 percent CI: 0.61-1.33) after adjusting for age, race, education, dental care utilization, and smoking status. CONCLUSIONS In this sample, a history of breast cancer does not significantly impact periodontal health, self-perceived oral health, and dental care utilization. However, efforts should be made to assure that breast cancer survivors have dental insurance.

Oral health-related concerns, behavior, and communication with health care providers of patients with breast cancer: impact of different treatments

AIM The objectives are to compare responses of breast cancer (BCa) treatment groups (chemotherapy, tamoxifen, and aromatase inhibitors (AIs) to each other and a control regarding (a) subjective oral health, (b) oral health-related behaviors, (c) oral health-related concerns, and (d) communication with health care providers. METHODS Survey data were collected from 140 postmenopausal BCa patients and 41 healthy postmenopausal control respondents. RESULTS BCa patients reported on average more frequent mouth sores/mucositis (5-point scale with 1 = never: 1.63 vs. 1.14; p < .01), glossadynia (1.60 vs. 1.07; p < .01), xerostomia (2.48 vs. 1.40; p < .01), and dysgeusia (2.10 vs. 1.46; p < .01) than the control respondents. Patients undergoing chemotherapy were more aware that cancer treatment can affect their oral health than patients on tamoxifen/AI (93% vs. 55%/56%; p < .001). BCa patients reported being more frequently informed by oncologists about oral health-related effects of cancer treatment than by dentists. Oncologists/nurses were more likely to communicate about oral health-related treatment effects with patients undergoing chemotherapy than patients on tamoxifen or AIs. Few BCa patients perceived dentists as knowledgeable about cancer treatment-related oral concerns and trusted them less than oncologists. CONCLUSIONS BCa treatments impact oral health. Low percentages of BCa patients had received specific information about impacts of BCa treatments on oral health from their dentists.

A Web-Based Decision Tool to Improve Contraceptive Counseling for Women With Chronic Medical Conditions: Protocol For a Mixed Methods Implementation Study

Background Women with chronic medical conditions, such as diabetes and hypertension, have a higher risk of pregnancy-related complications compared with women without medical conditions and should be offered contraception if desired. Although evidence based guidelines for contraceptive selection in the presence of medical conditions are available via the United States Medical Eligibility Criteria (US MEC), these guidelines are underutilized. Research also supports the use of decision tools to promote shared decision making between patients and providers during contraceptive counseling. Objective The overall goal of the MiHealth, MiChoice project is to design and implement a theory-driven, Web-based tool that incorporates the US MEC (provider-level intervention) within the vehicle of a contraceptive decision tool for women with chronic medical conditions (patient-level intervention) in community-based primary care settings (practice-level intervention). This will be a 3-phase study that includes a predesign phase, a design phase, and a testing phase in a randomized controlled trial. This study protocol describes phase 1 and aim 1, which is to determine patient-, provider-, and practice-level factors that are relevant to the design and implementation of the contraceptive decision tool. Methods This is a mixed methods implementation study. To customize the delivery of the US MEC in the decision tool, we selected high-priority constructs from the Consolidated Framework for Implementation Research and the Theoretical Domains Framework to drive data collection and analysis at the practice and provider level, respectively. A conceptual model that incorporates constructs from the transtheoretical model and the health beliefs model undergirds patient-level data collection and analysis and will inform customization of the decision tool for this population. We will recruit 6 community-based primary care practices and conduct quantitative surveys and semistructured qualitative interviews with women who have chronic medical conditions, their primary care providers (PCPs), and clinic staff, as well as field observations of practice activities. Quantitative survey data will be summarized with simple descriptive statistics and relationships between participant characteristics and contraceptive recommendations (for PCPs), and current contraceptive use (for patients) will be examined using Fisher exact test. We will conduct thematic analysis of qualitative data from interviews and field observations. The integration of data will occur by comparing, contrasting, and synthesizing qualitative and quantitative findings to inform the future development and implementation of the intervention. Results We are currently enrolling practices and anticipate study completion in 15 months. Conclusions This protocol describes the first phase of a multiphase mixed methods study to develop and implement a Web-based decision tool that is customized to meet the needs of women with chronic medical conditions in primary care settings. Study findings will promote contraceptive counseling via shared decision making and reflect evidence-based guidelines for contraceptive selection. Trial Registration ClinicalTrials.gov NCT03153644; https://clinicaltrials.gov/ct2/show/NCT03153644 (Archived by WebCite at http://www.webcitation.org/6yUkA5lK8)