- Browse by Subject
Browsing by Subject "Bone Diseases, Metabolic"
Now showing 1 - 3 of 3
Results Per Page
Sort Options
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 Proceedings of the 2021 Santa Fe Bone Symposium: Advances in the Management of Osteoporosis and Metabolic Bone Diseases(Elsevier, 2022) Lewiecki, E. Michael; Anderson, Paul A.; Bilezikian, John P.; Binkley, Neil; Cheung, Angela M.; Imel, Erik A.; Krueger, Diane; McClung, Michael R.; Miller, Paul D.; Rothman, Micol S.; Medicine, School of MedicineThe 2021 Virtual Santa Fe Bone Symposium was held August 5-8, with over 300 registered attendees from throughout the USA, and at least 18 other countries. This annual meeting focuses on applying advances in basic science and clinical research to the care of patients with osteoporosis and those with inherited and acquired disorders of bone metabolism. Participants represented a broad range of medical disciplines with an interest in skeletal diseases. These included physicians of many specialties and practice settings, fellows, advanced practice providers, fracture liaison service (FLS) coordinators, clinical researchers, and bone density technologists. There were lectures, case presentations, and panel discussions, all followed by interactive discussions. Breakout sessions included an FLS workshop, Bone Health TeleECHO workshop, special interest groups, meet-and-greet the faculty, and satellite symposia. The agenda covered topics of interest such as strategies for the use of osteoanabolic therapy, prevention of periprosthetic fractures, management of atypical femur fractures, what we know and don't know about vitamin D, advances in the use of dual-energy X-ray absorptiometry in the assessment of skeletal health, controversies and conundrums in osteoporosis care, skeletal health in transgender patients, management of patients with hypophosphatasia and hypophosphatemia, and treat-to-target approaches for managing patients with osteoporosis. The Proceedings of the 2021 Virtual Santa Fe Bone Symposium consists of highlights of each presentation with current strategies for optimizing the care of patients with skeletal disorders.Item Women have enhanced bone loss associated with phosphaturia and CD4+ cell restoration during initial antiretroviral therapy(Wolters Kluwer, 2018-11-13) Kalayjian, Robert C.; Albert, Jeffrey M.; Cremers, Serge; Gupta, Samir K.; McComsey, Grace A.; Klingman, Karin L.; Fichtenbaum, Carl J.; Brown, Todd T.; Taiwo, Babafemi O.; Medicine, School of MedicineOBJECTIVE: We compared bone mineral density (BMD) changes and their correlates, between men and women participating in two randomized trials of initial [antiretroviral therapy (ART)] regimens, with or without tenofovir disoproxil fumarate (TDF). METHODS: Covariates in linear regression models of 48-week hip and spine %BMD changes, by dual energy X-ray absorptiometry, included baseline and 48-week changes in plasma viral load, CD4 cells, plasma C-terminal telopeptide, procollagen 1 N-terminal propeptide and glomerular filtration rates, and the 48-week area under the curve of fractional excretion of phosphate. RESULTS: Despite overall hip and spine BMD declines of 2.8 and 2.9%, respectively, plasma viral load suppression to less than 50 vs. at least 50 copies/ml was associated 1.0% (P = 0.02) and 0.8% (P = 0.01) less BMD decline. Women had lower baseline spine (P = 0.04; n = 59 women, 418 men) and hip BMD (P = 0.01) in adjusted models, with 1.7% more hip decline on ART than men (P = 0.001). Serum phosphate was positively associated with baseline spine BMD in women (P = 0.03) but not men, and area under the curve of fractional excretion of phosphate was negatively associated with spine BMD changes, particularly in women randomized to TDF regimens (P = 0.03 and 0.054 for interactions by sex, and randomization to TDF vs. non-TDF regimens, respectively; n = 44 women, 326 men). Women also had 0.6% (P = 0.004) more hip BMD decline than men associated with each 100 CD4 cells/μl increase on ART (P = 0.02; n = 49 women, 379 men). CONCLUSION: Women randomized to TDF-containing ART had accentuated spine loss associated with phosphaturia, and accentuated hip loss associated with CD4 restoration, regardless of TDF exposure. Viral load suppression reduced bone loss.