Osteocalcin improves glucose tolerance, insulin sensitivity and secretion in older male mice.

Osteocalcin deficient mice (OC-/-), on a mixed 129/BL6J background, were reported to show glucose intolerance, insulin insensitivity and reduced insulin secretion at 1-6 mos of age. This is controversial as two studies in OC-/- mice on different backgrounds (C3H/BL6 (5-6 mos.) and C57BL/6N (5 and 9 mos.)) found no effect on glucose metabolism. To determine the role of OC in glucose metabolism we conducted glucose tolerance tests (GTT), insulin tolerances tests (ITT) and glucose stimulated insulin secretion (GSIS) on 6 and 9.5 month-old male OC-/- and OC+/+ mice on a pure C57BL/6J background and fed a normal chow diet. All results were analyzed with a two-way repeated measures ANOVA. The GTT results showed no effect on males at 6 months of age but glucose intolerance was significantly increased (p < 0.05) in male OC-/- mice at 9.5 months of age. The ITT results indicated significantly increased insulin resistance in male OC-/- mice. Glucose stimulated insulin secretion (GSIS) showed insulin significantly (p < 0.05) reduced in OC-/- at several time points. Mouse Osteocalcin injected into OC-/- mice decreased the glucose level. Our results confirm the role of OC in glucose metabolism and insulin sensitivity and demonstrate a role in insulin secretion in older male mice on a C57BL/6J background. Differences in background, age, or experimental procedures could explain controversial results. A delayed onset of the effect of OC on glucose metabolism at 9.5 months in male C57BL/6J mice highlights the importance of background on phenotype. Consideration of genetic background and age may be beneficial for human studies on osteocalcin and glucose homeostasis and may be relevant to the elderly where osteocalcin is reduced.

Utilization Trends of Total Ankle Arthroplasty and Ankle Fusion for Tibiotalar Osteoarthritis: A Nationwide Analysis of the United States Population.

Introduction: Studies evaluating utilization and trends of total ankle arthroplasty (TAA) and ankle fusion (AF) are sparse. The purpose of this study was to use a nationwide administrative claims database to compare baseline demographics between TAA and ankle arthrodesis and to determine whether patients who had a TAA have increased rates of: (1) utilization, (2) in-hospital length of stay (LOS), and (3) costs of care. Methods: PearlDiver, a nationwide claims database was queried from 2005 to December 2013 for all patients who underwent primary TAA or AF for the treatment of osteoarthritis of the ankle and foot. Baseline demographics of age, sex, geographic distribution, and the prevalence of comorbidities comprising the Elixhauser comorbidity index (ECI) were compared between patients who had TAA and AF. Linear regression was used to compare differences in utilization and in-hospital LOS between the 2 cohorts during the study interval. Annual charges and reimbursement rates for TAA were assessed during the study period. A P value less than .05 was considered to be statistically significant. Results: A total of 21 433 patients undergoing primary TAA (n = 7126) and AF (n = 14 307) were included. Patients undergoing TAA had significantly greater ECI driven by arrythmias, congestive heart failure, diabetes mellitus, electrolyte/fluid disorders, iron deficiency anemia than patients undergoing AF (P < .001). From 2005 to 2013, TAA utilization increased from 21.5% to 49.4% of procedures (P < .0001). There was reduced in-hospital LOS over the time interval for patients with TAA compared with AF (2.15 days vs. 3.11 days, P < .0001). Total ankle arthroplasty reimbursements remained stable while charges per patient increased significantly from $40 203.48 in 2005 to doubling by the end of 2013 to $86 208.59 (P < .0001). Conclusion: This study demonstrated increased use of TAA compared to AF showing decreased in-hospital LOS and increased cost of care with stagnant reimbursement rates.Level of Evidence: Level III.

Association of Opioid Use Disorder on Postoperative Outcomes Following Lumbar Laminectomy: A Nationwide Retrospective Analysis of the Medicare Population.

BACKGROUND: Research focused on the association of opioid use disorder (OUD) on postoperative outcomes in patients undergoing primary lumbar laminectomy is lacking. This study aims to observe the impact of OUD on (1) hospital length of stay (LOS), (2) readmission rates, (3) medical complications, and (4) health care expenditures. METHODS: A retrospective query was performed using a nationwide claims database from January 2005 to March 2014 for all patients who underwent lumbar laminectomy, yielding a total of 131,635 patients. The study cohort included 3515 patients with OUD, while 128,120 patients served as the comparison cohort. Multivariate binomial logistic regression analyses were used to determine the association of OUD on readmission rates and medical complications, whereas Welch's t tests were used to compare LOS and health care expenditures. A P value less than 0.001 was considered statistically significant. RESULTS: Patients with OUD undergoing lumbar laminectomy had significantly longer hospital LOS (3.68 vs 1.13 days, P < 0.0001). Readmission rates were significantly higher (14.57% vs 7.39%, OR: 1.73, P < 0.0001) in patients who had an OUD. The study cohort was found to have higher incidence and odds (32.36% vs 9.76%, OR: 3.53, P < 0.0001) of 90-day medical complications and total global 90-day episode of care reimbursement rates ($13,635.81 vs $8131.20, P < 0.0001) compared with their counterparts. CONCLUSIONS: This study demonstrates OUD to be associated with longer hospital LOS, increased rates of 90-day readmissions, medical complications, and health care expenditures following lumbar laminectomy. CLINICAL RELEVANCE: Results indicate that OUD is associated with worse outcomes following lumbar laminectomy.

An osteocalcin-deficient mouse strain without endocrine abnormalities.

Osteocalcin (OCN), the most abundant noncollagenous protein in the bone matrix, is reported to be a bone-derived endocrine hormone with wide-ranging effects on many aspects of physiology, including glucose metabolism and male fertility. Many of these observations were made using an OCN-deficient mouse allele (Osc-) in which the 2 OCN-encoding genes in mice, Bglap and Bglap2, were deleted in ES cells by homologous recombination. Here we describe mice with a new Bglap and Bglap2 double-knockout (dko) allele (Bglap/2p.Pro25fs17Ter) that was generated by CRISPR/Cas9-mediated gene editing. Mice homozygous for this new allele do not express full-length Bglap or Bglap2 mRNA and have no immunodetectable OCN in their serum. FTIR imaging of cortical bone in these homozygous knockout animals finds alterations in the collagen maturity and carbonate to phosphate ratio in the cortical bone, compared with wild-type littermates. However, µCT and 3-point bending tests do not find differences from wild-type littermates with respect to bone mass and strength. In contrast to the previously reported OCN-deficient mice with the Osc-allele, serum glucose levels and male fertility in the OCN-deficient mice with the Bglap/2pPro25fs17Ter allele did not have significant differences from wild-type littermates. We cannot explain the absence of endocrine effects in mice with this new knockout allele. Possible explanations include the effects of each mutated allele on the transcription of neighboring genes, or differences in genetic background and environment. So that our findings can be confirmed and extended by other interested investigators, we are donating this new Bglap and Bglap2 double-knockout strain to the Jackson Laboratories for academic distribution.