The Effects of Signaling-Selective Parathyroid Hormone Analogs on Osteoporotic Osteocyte Apoptosis

Objectives: To compare the effects of signaling-selective parathyroid hormone analogs [G1, R19]hPTH(1–28) [GR(1–28)] and [G1, R19]hPTH(1–34) [GR(1–34)] on osteoporotic osteocyte apoptosis, and to explore the mechanism of the anti-osteoporotic difference. Methods: The osteoporosis model was established in eighty adult female C57BL/6 mice aged 12 weeks. The mice were subcutaneously administered with GR(1–28) and GR(1–34) 5 days per week for 8 weeks. Bilateral femur samples were collected at 4 and 8 weeks, and micro-computed tomography (CT), H&E staining and immunohistochemical staining analyses were performed. Results: From micro-CT analysis, GR(1–34) increased proximal femoral bone mineral density (BMD) and relative bone volume (BV/TV), which was higher than GR(1–28) did. In addition, more trabecular number (Tb.N), thinner trabecular thickness (Tb.Th) and wider trabecular separation (Tb.Sp) were measured at week 8 using GR(1–34). From H&E and immunohistochemical staining, a stronger apoptosis inhibition was induced by GR(1–34) with more Bcl-2 secretion but less Bax expression, as opposed to GR(1–28). Conclusions: GR(1–34) shows better anti-osteoporotic effects than GR(1–28), which appears to be attributed to the activation of the PLC-independent PKC signaling pathway triggered by the former, inhibiting osteocyte apoptosis through up-regulation of Bcl-2 and down-regulation of Bax to increase bone mass and improving trabecular bone microstructure to enhance bone quality by reducing trabecular number, increasing trabecular thickness and trabecular space.

Short-term success of proximal bone stock preservation in short hip stems: a systematic review of the literature

Total hip arthroplasty is performed more frequently in younger patients nowadays, making long-term bone stock preservation an important topic. A mechanism for late implant failure is periprosthetic bone loss, caused by stress shielding around the hip stem due to different load distribution. Short stems are designed to keep the physical loading in the proximal part of the femur to reduce stress shielding. The aim of this review is to give more insight into how short and anatomic stems behave and whether they succeed in preservation of proximal bone stock. A systematic literature search was performed to find all published studies on bone mineral density in short and anatomic hip stems. Results on periprosthetic femoral bone mineral density, measured with dual-energy X-ray absorptiometry (DEXA), were compiled and analysed per Gruen zone in percentual change. A total of 29 studies were included. In short stems, Gruen 1 showed bone loss of 5% after one year (n = 855) and 5% after two years (n = 266). Gruen 7 showed bone loss of 10% after one year and –11% after two years. In anatomic stems, Gruen 1 showed bone loss of 8% after one year (n = 731) and 11% after two years (n = 227). Gruen 7 showed bone loss of 14% after one year and 15% after two years. Short stems are capable of preserving proximal bone stock and have slightly less proximal bone loss in the first years, compared to anatomic stems. Cite this article: EFORT Open Rev 2021;6:1040-1051. DOI: 10.1302/2058-5241.6.210030

Serum N-terminal telopeptide of type I collagen as a biomarker for predicting bone density loss in patients with Crohn disease

Background The serum N-terminal telopeptide of type I collagen (NTx) is significantly higher in patients with Crohn disease (CD) than in healthy individuals and patients with ulcerative colitis. This study aimed to investigate whether an elevated serum NTx level is a risk predictor of osteoporosis in patients with CD. Methods Based on whether the femoral Z-score decreased over a 2-year period, 41 CD patients were divided into the ΔZ-score <0 group (Z-score decreased) and the ΔZ-score ≥0 group (Z-score did not decrease). The risk predictors of a femoral Z-score decrease were examined. Furthermore, we investigated the correlations between the ΔZ-score (which represents the change in the Z-score over a 2-year period) and the mean levels of biomarkers, including the Crohn Disease Activity Index (CDAI), serum albumin, C-reactive protein, and bone metabolism markers (including NTx) measured initially (i.e., in our previous study) and 2 years later (present study). The relationships between anti-tumor necrosis factor α (anti-TNF-α) therapy and serum NTx levels were also examined. Results Although there was no correlation between the mean CDAI and the ΔZ-score, the mean serum NTx and albumin levels were significantly correlated with the ΔZ-score (P<0.01 and P = 0.02, respectively). Furthermore, the femoral Z-score tended to be lower in the anti-TNF-α administration group than in the non-administration group. Conclusions These observations indicated that an elevated serum NTx could be a useful marker for predicting a decrease in the femoral bone mineral density in CD patients. Anti-TNF-α therapy maintained an elevated serum NTx level, suggesting that treatment with anti-TNF-α may help control increased bone resorption in CD patients.

NAFLD and liver fibrosis are not associated with reduced femoral bone mineral density in the general US population

Context It is still debated whether nonalcoholic fatty liver disease (NAFLD) may be a risk factor for reduced bone mineral density (BMD), and it is not known whether liver fibrosis, which is the major predictor of future development of liver-related events in patients with NAFLD, has an influence on BMD. Objective To assess whether liver steatosis and fibrosis are associated with reduced BMD in the general US population. Design Cross-sectional analysis of the population-based 2017-2018 cycle of the National Health and Nutrition Examination Survey (NHANES), in which vibration controlled transient elastography (VCTE) and dual-energy x-ray absorptiometry (DXA) of the femoral neck were simultaneously available. Controlled attenuation parameter (CAP) ≥ 274 dB/m was considered indicative of liver steatosis, while a median liver stiffness measurement (LSM) ≥ 8 kPa indicated the presence of significant liver fibrosis. Patients We included all participants older than 50 with reliable VCTE and femoral neck DXA results (925 men and 859 women). Main Outcomes Femoral neck BMD values indicative of osteopenia or osteoporosis. Results Steatosis and significant fibrosis were highly prevalent in the studied population, being present in 53.1% and 9.6%of men and 44.2% and 8.0% of women, respectively. In univariate analysis, liver steatosis was associated with a lower prevalence of osteoporosis in both men and women, while no difference was noted according to the degree of liver fibrosis. After adjustment for potential confounders including age, BMI, race-ethnicity, cigarette smoke and diabetes, neither CAP, nor LSM were significantly associated with reduced BMD in both sexes. Conclusions Liver steatosis and fibrosis are not associated with femoral DXA-based diagnosis of osteopenia or osteoporosis in the US population older than 50 years.