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Item Bone mineral density reductions after tenofovir disoproxil fumarate initiation and changes in phosphaturia: a secondary analysis of ACTG A5224s(Oxford Academic, 2017-07-01) Gupta, Samir K.; Yeh, Eunice; Kitch, Douglas W.; Brown, Todd T.; Venuto, Charles S.; Morse, Gene D.; Ha, Belinda; Melbourne, Kathleen; McComsey, Grace A.; Medicine, School of MedicineBackground: It is unknown if the greater reductions in bone mineral density (BMD) associated with initiation of tenofovir disoproxil fumarate compared with abacavir in previously untreated HIV-infected participants in the ACTG A5224s clinical trial were associated with potentially worsening tenofovir-related phosphaturia. Methods: We correlated changes in BMD at the hip and spine with changes in phosphaturia [transtubular reabsorption of phosphorus (TRP) and tubular maximum phosphate reabsorption per glomerular filtration rate (TmP/GFR)] from entry through week 96 in those initiating tenofovir ( n = 134) versus abacavir ( n = 135) with efavirenz or atazanavir/ritonavir in A5224s. We also correlated changes in BMD with tenofovir AUC measured between weeks 4 and 24. Results: Changes in TRP and TmP/GFR through week 96 between the tenofovir and abacavir arms were not significantly different (both P ≥ 0.70) and did not differ with use of efavirenz versus atazanavir/ritonavir. There were no significant correlations between changes in either TRP or TmP/GFR and with either hip or spine BMD in the tenofovir arms. Tenofovir AUC was significantly correlated with changes in hip BMD, but not spine BMD, at week 24 ( r = -0.22, P = 0.028) and week 48 ( r = -0.26, P = 0.010), but not at week 96 ( r = -0.14, P = 0.18). Conclusions: Changes in phosphaturia were not different between the tenofovir and abacavir arms in A5224s. Changes in hip and spine BMD with tenofovir were not related to changes in phosphaturia. However, tenofovir exposure was weakly associated with changes in hip BMD through week 48.Item Digital Radiographic Analysis of Mineral Density of Adjacent Alveolar Bone in Relation to the Molar Translation Rate After Use of Retromolar Implant Anchorage(1997) Sim, Yeongsuk; Roberts, W. Eugene; Analoui, Mostafa; Hohlt, William F.; Katona, Thomas R.; Shanks, James C., Jr.Molar translation using retromolar implants provides an unique opportunity to measure the rate of orthodontic tooth movement, because implants do not permit any reactive movement from the force. Contrast-corrected digital radiography was utilized to investigate the rate of molar translation related to the mineral density of adjacent alveolar bone. It was hypothesized that the rate of molar translation was inversely correlated with bone mineral density ahead of the moving tooth. Periapical radiographs were obtained every six months during 24 months of active treatment of eight patients (age: 24 to 48 years). Distance from three reference points (crown tip, mid-root, apex) and mineral density of four circular areas in front of the translating molar were analyzed for correlation. The primary method of analysis was the use of Pearson correlation coefficients between rate change and bone mineral density, and between rate change and age. The results showed that rate change of molar translation at the root apex was inversely correlated to the mineral density of adjacent alveolar bone. The correlations were not significant when examining the rate over the first six months; however, the correlations were significant after the second follow-up evaluation at 12 months. The correlation was also significant when using the overall means up to last follow-up visit. However, patient age was not significantly related to the rate of molar translation in this study.Item Effect of kidney donation on bone mineral metabolism(Public Library of Science, 2020-07-07) Hiemstra, Thomas F.; Smith, Jane C.; Lim, Kenneth; Xu, Dihua; Kulkarni, Shreya; Bradley, J. Andrew; Paapstel, Kaido; Schoenmakers, Inez; Bradley, John R.; Tomlinson, Laurie; McEniery, Carmel M.; Wilkinson, Ian B.; Medicine, School of MedicineKidney donation results in reductions in kidney function and lasting perturbations in phosphate homeostasis, which may lead to adverse cardiovascular sequelae. However, the acute effects of kidney donation on bone mineral parameters including regulators of calcium and phosphate metabolism are unknown. We conducted a prospective observational controlled study to determine the acute effects of kidney donation on mineral metabolism and skeletal health. Biochemical endpoints were determined before and after donation on days 1, 2 and 3, 6 weeks and 12 months in donors and at baseline, 6 weeks and 12 months in controls. Baseline characteristic of donors (n = 34) and controls (n = 34) were similar: age (53±10 vs 50±14 years, p = 0.33), BMI (26.3±2.89 vs 25.9±3.65, p = 0.59), systolic BP (128±13 vs 130±6 mmHg, p = 0.59), diastolic BP (80±9 vs 81±9 mmHg, p = 0.68) and baseline GFR (84.4±20.2 vs 83.6±25.2 ml/min/1.73m2, p = 0.89). eGFR reduced from 84.4±20.2 to 52.3±17.5 ml/min/1.73m2 (p<0.001) by day 1 with incomplete recovery by 12 months (67.7±22.6; p = 0.002). Phosphate increased by day 1 (1.1(0.9–1.2) to 1.3(1.1–1.4) mmol/L, p <0.001) but declined to 0.8(0.8–1.0) mmol/L (p<0.001) before normalizing by 6 weeks. Calcium declined on day 1 (p = 0.003) but recovered at 6 weeks or 12 months. PTH and FGF-23 remained unchanged, but α-Klotho reduced by day 1 (p = 0.001) and remained low at 6 weeks (p = 0.02) and 1 year (p = 0.04). In this study, we conclude that kidney donation results in acute disturbances in mineral metabolism characterised by a reduced phosphate and circulating α-Klotho concentration without acute changes in the phosphaturic hormones FGF23 and PTH.Item Enhancing Root Caries Lesion Prevention By Combining Two American Dental Association-Recommended Preventive Agents(2022) Almudahi, Abdulellah; Duarte, Simone; Hara, Anderson; Cook, N.BlainePurpose: This in vitro study aims to analyze the effect of combining two ADA-recommended professionally applied 1:1 Chlorhexidine/Thymol varnish ((Cervitec Plus)) and professionally prescribed 5,000 ppm fluoride toothpaste ((PreviDent 5000 Plus)) on reducing lesion depth and increasing mineral content Materials & Methods: Forty-eight dentin specimens were randomly distributed into four treatment groups (n=12 per treatment). Biofilms of Streptococcus mutans and Candida albicans were created on the polished surfaces of bovine root dentin specimens (n=12 per treatment). 1:1 Chlorhexidine/Thymol varnish was applied once then the tested 5,000 ppm fluoride toothpaste was applied for 120 seconds twice daily over the course of 2 days. Tested groups were: (1) 1:1 Chlorhexidine/Thymol varnish ((Cervitec Plus)) (C/T). (2) 5,000 ppm F toothpaste ((PreviDent 5000 Plus)) (F). (3) Combination of 1:1 Chlorhexidine/Thymol varnish ((Cervitec Plus)) & 5000 ppm F toothpaste ((PreviDent 5000 Plus)) (C/T+F). (4) Deionized water (DIW) as control group. Biofilms were analyzed for biofilm dry weight. Dentin specimens were analyzed using transversal microradiography (TMR) for mineral content change and lesion depth. PH data was analyzed using two-way ANOVA. Total biofilm dry weight data was analyzed using one-way ANOVA. Integrated mineral loss and lesion depth data was analyzed using two-way ANOVA All pair-wise comparisons from ANOVA analysis were made using Fisher’s Protected Least Significant Differences to control the overall significance level at 5%. Results: Treatment with (C/T+F) resulted in higher mean pH values compared to the control group (DIW) and (F) group. The average pH values of group (C/T) were not statistically different than group (C/T+F). the biomass of the combined S. mutans & C. albicans biofilm among all the groups were not significantly different. (DIW) presented significantly deeper lesions for both surfaces (sound &demineralized) when compared to (F) (P=0.0118), (C/T) (P=0.0002), and (C/T+F) (P<.0001). The sound surfaces for the specimens for group (C/T) and Group (F) showed superficial lesion depth. However, the sound surfaces of specimens treated with (C/T+F) showed the most superficial depth. Due to mineral gain, the demineralized surfaces of the specimens of both (C/T) & (C/T+F) showed a decrease in the lesion depth. Conclusion: Within the limitations of our study. The combination of 5,000 ppm fluoride toothpaste and CHX/Thymol had no significant effect on mineral content. However, the combination had a considerable effect on lesion depth reduction.Item Missense Mutations in LRP5 Associated with High Bone Mass Protect the Mouse Skeleton from Disuse- and Ovariectomy-Induced Osteopenia(Public Library of Science (PLoS), 2015) Niziolek, Paul J.; Bullock, Whitney; Warman, Matthew L.; Robling, Alexander G.; Department of Anatomy & Cell Biology, IU School of MedicineThe low density lipoprotein receptor-related protein-5 (LRP5), a co-receptor in the Wnt signaling pathway, modulates bone mass in humans and in mice. Lrp5 knock-out mice have severely impaired responsiveness to mechanical stimulation whereas Lrp5 gain-of-function knock-in and transgenic mice have enhanced responsiveness to mechanical stimulation. Those observations highlight the importance of Lrp5 protein in bone cell mechanotransduction. It is unclear if and how high bone mass-causing (HBM) point mutations in Lrp5 alter the bone-wasting effects of mechanical disuse. To address this issue we explored the skeletal effects of mechanical disuse using two models, tail suspension and Botulinum toxin-induced muscle paralysis, in two different Lrp5 HBM knock-in mouse models. A separate experiment employing estrogen withdrawal-induced bone loss by ovariectomy was also conducted as a control. Both disuse stimuli induced significant bone loss in WT mice, but Lrp5 A214V and G171V were partially or fully protected from the bone loss that normally results from disuse. Trabecular bone parameters among HBM mice were significantly affected by disuse in both models, but these data are consistent with DEXA data showing a failure to continue growing in HBM mice, rather than a loss of pre-existing bone. Ovariectomy in Lrp5 HBM mice resulted in similar protection from catabolism as was observed for the disuse experiments. In conclusion, the Lrp5 HBM alleles offer significant protection from the resorptive effects of disuse and from estrogen withdrawal, and consequently, present a potential mechanism to mimic with pharmaceutical intervention to protect against various bone-wasting stimuli.Item Modifications in Bone Matrix of Estrogen-Deficient Rats Treated with Intermittent PTH(Hindawi Publishing Corporation, 2015-01-28) Pacheco-Costa, Rafael; Campos, Jenifer Freitas; Katchburian, Eduardo; de Medeiros, Valquíria Pereira; Nader, Helena Bonciani; Nonaka, Keico Okino; Plotkin, Lilian Irene; Reginato, Rejane Daniele; Department of Anatomy & Cell Biology, IU School of MedicineBone matrix dictates strength, elasticity, and stiffness to the bone. Intermittent parathyroid hormone (iPTH), a bone-forming treatment, is widely used as a therapy for osteoporosis. We investigate whether low doses of intermittent PTH (1-34) change the profile of organic components in the bone matrix after 30 days of treatment. Forty 6-month-old female Wistar rats underwent ovariectomy and after 3 months received low doses of iPTH administered for 30 days: daily at 0.3 µg/kg/day (PTH03) or 5 µg/kg/day (PTH5); or 3 times per week at 0.25 µg/kg/day (PTH025). After euthanasia, distal femora were processed for bone histomorphometry, histochemistry for collagen and glycosaminoglycans, biochemical quantification of sulfated glycosaminoglycans, and hyaluronan by ELISA and TUNEL staining. Whole tibiae were used to estimate the bone mineral density (BMD). Histomorphometric analysis showed that PTH5 increased cancellous bone volume by 6% over vehicle-treated rats. In addition, PTH5 and PTH03 increased cortical thickness by 21% and 20%, respectively. Tibial BMD increased in PTH5-treated rats and this group exhibited lower levels of chondroitin sulfate; on the other hand, hyaluronan expression was increased. Hormonal administration in the PTH5 group led to decreased collagen maturity. Further, TUNEL-positive osteocytes were decreased in the cortical compartment of PTH5 whereas administration of PTH025 increased the osteocyte death. Our findings suggest that daily injections of PTH at low doses alter the pattern of organic components from the bone matrix, favoring the increase of bone mass.Item Pyk2 deficiency enhances bone mass during midpalatal suture expansion(Wiley, 2020-11) Sun, Jun; Eleniste, Pierre P.; Utreja, Achint; Turkkahraman, Hakan; Liu, Sean Shih-Yao; Bruzzaniti, Angela; Prosthodontics, School of DentistryOBJECTIVE: To determine if Pyk2 deficiency increases midpalatal suture bone mass and preserves sutural integrity after maxillary expansion. SETTING AND SAMPLE: Thirty-six male Pyk2 knockout (KO) and control (WT) mice at 6 weeks of age. MATERIALS AND METHODS: Mice received nickel-titanium spring expanders delivering 0 g (no intervention control), 10 or 20 g force for 14 days. High-resolution micro-CT was used to determine bone volume/tissue volume (BV/TV), sutural width and intermolar width. Effects on osteoclasts, chondrocytes and suture morphology were determined by histomorphometry. RESULTS: Pyk2-KO controls (0 g) had 7% higher BV/TV compared with WT controls. Expanded Pyk2-KO maxillae also exhibited 12% (10 g) and 18% (20 g) higher BV/TV than WT mice. Although bone loss following expansion occurred in both genotypes, BV/TV was decreased to a greater extent in WT maxillae (-10% at 10g; -22% at 20 g) compared with Pyk2-KO maxillae (-11% only at 20 g). Expanded WT maxillae also showed a greater increase in sutural width, intermolar width and fibrous connective tissue width compared with expanded Pyk2-KO maxillae. Moreover, osteoclast number was increased 77% (10 g) and 132% (20 g) in expanded WT maxillae, but remained unchanged in expanded Pyk2-KO, compared to their respective controls. Cartilage area and chondrocyte number were increased to the same extent in expanded WT and Pyk2-KO sutures. CONCLUSIONS: These findings suggest that midpalatal suture expansion increases osteoclast formation in WT but not Pyk2-KO mice, leading to higher BV/TV in expanded Pyk2-KO maxillae. These studies suggest Pyk2-targeted strategies may be beneficial to increase bone density and preserve sutural integrity during maxillary expansion.