The Relationship Between Osteoporosis and Intestinal Microbes in the Henan Province of China

Osteoporosis (OP) is a chronic disease in the elderly, and China is entering an aging demographic trend. In recent years, increasing evidence has demonstrated that probiotics can treat osteoporosis. This study aimed to explore the relevant mechanisms and to validate the beneficial effect on osteoporosis by high-throughput metagenome-wide gene sequencing in humans. In this study, compared with controls, several species had altered abundances, and specific functional pathways were found in the OP group. At the species level, the species that had increased in OP individuals were positively correlated to bone resorption markers and negatively correlated to 25-OH-D3 and bone formation markers, with Streptococcus sanguinis showing the strongest relevance, followed by Streptococcus gordonii, Actinomyces odontolyticus, and Olsenella unclassified. Additionally, Actinomyces graevenitzii, enriched in the OP group, was positively correlated to inflammation indicators that included white blood cell (WBC), neutrophil count (NEC), and the neutrophil-to-lymphocyte ratio (NLR) (p < 0.05). Conversely, the levels of Akkermansia muciniphila, Bacteroides eggerthii, Bacteroides fragilis, Bacteroides uniformis, and Butyricimonas synergistic were increased in the control group, which had a negative correlation with bone resorption markers and positive correlation with bone formation markers and 25-OH-D3. Additionally, Bacteroides fragilis had a negative correlation with inflammation indicators (WBC, NEC, and NLR) and the above pathways (p < 0.05). Functional prediction revealed that 106 metabolic pathways, enriched in the OP group, were significantly higher than in the control group (p < 0.05). In particular, pathways related to LPS biosynthesis, phytate degradation, lactate acid, and ethanol fermentation were more abundant in the OP group than in the control and were positively related to WBC and NEC. Taken together, several species with altered abundances and specific functional pathways were found in OP individuals. The role of phytases in OP provides novel epidemiological evidence to elucidate the underlying microbiota-relevant mechanisms in bone mineralization and should be explored further.

Iron deficiency and high-intensity running interval training do not impact femoral or tibial bone in young female rats

In the US, as many as 20% of recruits sustain stress fractures during basic training. In addition, approximately one-third of female recruits develop iron deficiency upon completion of training. Iron is a cofactor in bone collagen formation and vitamin D activation, thus we hypothesized iron deficiency may be contributing to altered bone microarchitecture and mechanics during 12-weeks of increased mechanical loading. Three-week old female Sprague Dawley rats were assigned to one of four groups: iron adequate sedentary, iron deficient sedentary, iron adequate exercise, and iron deficient exercise. Exercise consisted of high-intensity treadmill running (54 min 3×/week). After 12-weeks, serum bone turnover markers, femoral geometry and microarchitecture, mechanical properties and fracture toughness, and tibiae mineral composition and morphometry were measured. Iron deficiency increased the bone resorption markers C-terminal telopeptide type I collagen and tartate-resistant acid phosphatase 5b (TRAcP 5b). In exercised rats, iron deficiency further increased bone TRAcP 5b, while in iron adequate rats, exercise increased the bone formation marker procollagen type I N-terminal propeptide. In the femur, exercise increased cortical thickness and maximum load. In the tibia, iron deficiency increased the rate of bone formation, mineral apposition, and zinc content. These data show that the femur and tibia structure and mechanical properties are not negatively impacted by iron deficiency despite a decrease in tibiae iron content and increase in serum bone resorption markers during 12-weeks of high-intensity running in young growing female rats.

Factors Associated with Bone Mineral Density and Bone Resorption Markers in Postmenopausal HIV-Infected Women on Antiretroviral Therapy: A Prospective Cohort Study

The study aimed to determine factors associated with changes in bone mineral density (BMD) and bone resorption markers over two years in black postmenopausal women living with human immunodeficiency virus (HIV) on antiretroviral therapy (ART). Women (n = 120) aged > 45 years were recruited from Potchefstroom, South Africa. Total lumbar spine and left femoral neck (LFN) BMD were measured with dual energy X-ray absorptiometry. Fasting serum C-Telopeptide of Type I collagen (CTx), vitamin D and parathyroid hormone were measured. Vitamin D insufficiency levels increased from 23% at baseline to 39% at follow up. In mixed linear models serum CTx showed no change from baseline to end (p = 0.363, effect size = 0.09). Total and LFN BMD increased significantly over two years, but effect sizes were small. No significant change in spine BMD over time was detected (p = 0.19, effect size = 0.02). Age was significantly positively associated with CTx over time, and negatively with total and LFN BMD. Physical activity (PA) was positively associated with LFN BMD (p = 0.008). Despite a decrease in serum vitamin D, BMD and CTx showed small or no changes over 2 years. Future studies should investigate PA interventions to maintain BMD in women living with HIV.

Case Report: Severe Osteoporosis and Preventive Therapy in RNA Polymerase III-Related Leukodystrophy

RNA polymerase III (POLR3)-related leukodystrophy is an autosomal recessive form of leukodystrophy caused by homozygous or compound heterozygous mutations of the RNA polymerase III subunit genes, including subunit A (POLR3A). With respect to the manifestation triad, hypomyelination, hypodontia, and hypogonadotropic hypogonadism, it is also known as 4H leukodystrophy. Here, we report a 41-year-old woman of POLR3-related leukodystrophy by carrying compound heterozygous pathogenic variants of c.2554A>G (p.M852V) and c.2668G>T (p.V890F) in the POLR3A gene. She was amenorrheic and became a wheelchair user from the age of 15 years and suffered from multiple episodes of pathologic fractures, starting with a subtrochanteric fracture of the right femur after a tonic seizure at age 30 years. Head magnetic resonance imaging demonstrated hypomyelination and atrophies of the cerebellum, brainstem, and corpus callosum. Laboratory examination revealed a marked decrease of gonadotropins and estrogen, low bone density, and high bone resorption markers. Administration of anti-receptor activator of nuclear factor kappa-B ligand monoclonal antibody restored bone resorption markers to a normal level and prevented further pathological bone fractures. Our case emphasizes that osteoporosis should be recognized as a potential but serious complication in POLR3-related leukodystrophy. It may be feasible to prevent pathologic fractures by intensive osteoporosis therapy after endocrinological examinations and evaluation of bone metabolism.

The main clinical and diagnostic characteristics of patients with low back pain and sacroiliac joint diseases (results of the IOLANTA-II study)

Objective: to investigate the clinical and diagnostic characteristics of patients with low back pain in the presence of sacroiliac joint (SIJ) disease.Patients and methods. The investigation design involved three visits: V 1 (inclusion); V 2 (after 7 days), and V 3 (after 3 months); after the screening period, the investigation enrolled 259 patients aged 65.5 [62.5; 69.5] years; of them there were 165 (63.7%) women. At V 1 , according to magnetic resonance imaging findings, the patients were divided into two groups: 1) 157 patients without confirmed SIJ disease; 2) 102 patients with confirmed SIJ disease. During all visits, the investigators made general clinical and neurological examinations and assessed the intensity of pain syndrome according to a visual analogue scale (VAS) for pain in millimeters, a neuropathic pain component according to the DN4 questionnaire, by determining the blood parameters: transforming growth factor-β1 (TGF-β1), interleukin-1β (IL-1β), IL-6, Beta-Crosslaps, the indicator of bone matrix formation procollagen type 1 N-terminal propeptide (P1NP) and by estimating the urinary level of deoxypyridinoline.Results and discussion. At all visits, Group 2 patients with higher VAS pain scores had a pain history that was statistically significantly longer (p<0.001). The ANOVA analysis showed that the patients in Group 2 had statistically significantly higher values of TGF-β1, IL-1β, IL-6, and bone resorption markers than those in Group 1, which suggests the relationship between pain syndrome and the presence of an inflammatoryresorptive process in patients with SIJ disease.Conclusion. A high (39.4%) prevalence of SIJ disease was noted in patients over 60 years of age with low back pain. During the follow-up period, there was a decrease in bone resorption markers and cytokines; however, the SIJ disease group showed less pronounced changes with statistically significant differences in all parameters than in the non-SIJ disease group. It is advisable to consider an algorithm for diagnosing a patient over 60 years of age with low back pain, by mandatorily examining his/her SIJ. Treatment policy, including methods for correction with drugs, should be discussed based on the findings.

Comparison of Serum Level of Bone Resorption Markers with Bone Densitometry in Elderly Individuals in Port Harcourt, Rivers State

Introduction: This study concentrated on serum bone markers, N and C- telopeptide and tartrate resistant acid phosphatase (TRAP), and their concentrations were evaluated in the serum of elderly participants and compared with that of the young of the same gender. Markers for bone resorption are proteins, and they are mainly measured in the urine and serum, where they serve to assess bone turnover. Methodology: A cross-sectional prospective study conducted at the orthopaedic and Family Medicine Departments of the University of Port Harcourt Teaching Hospital, a public tertiary healthcare facility located in Choba and Alakahia communities of Obio/Akpor Local Government Areas of Rivers state, Nigeria, among elderly patients aged 60 years and above. Results: Considering the age of the test population, all the females were post-menopausal and no statistical difference was observed in relation to the results for gender in the study. Also, the plasma creatinine, calcium and albumin results of both controls and participants were within normal reference range. The study was necessitated by the fact that, in the environment of the study (Port Harcourt), elderly individuals frequently complain of bone pain, thus, the serum levels of the aforementioned bone resorption markers (N and C telopeptide and tartrate resistant acid phosphatase) was estimated among these elderly individuals, with the view that its outcome can help physicians to initiate protocols that will prevent the consequences of increased bone resorption, intervenes before bone becomes fragile and aid the prediction of osteoporosis. Conclusion: This study was able to establish that the serum levels of NTX, CTX and TRAP were increased in elderly participants above the age of sixty years than controls.