Oral and gut microbial profiling in periodontitis and Parkinson's disease.

Objectives: We tested the hypothesis that Parkinson's disease (PA) alters the periodontitis-associated oral microbiome. Method: Patients with periodontitis with Parkinson's disease (PA+P) and without PA (P) and systemically and periodontally healthy individuals (HC) were enrolled. Clinical, periodontal and neurological parameters were recorded. The severity of PA motor functions was measured. Unstimulated saliva samples and stool samples were collected. Next-generation sequencing of 16S ribosomal RNA (V1-V3 regions) was performed. Results: PA patients had mild-to-moderate motor dysfunction and comparable plaque scores as those without, indicating that oral hygiene was efficient in the PA+P group. In saliva, there were statistically significant differences in beta diversity between HC and PA+P (p = 0.001), HC and P (p = 0.001), and P and PA+P (p = 0.028). The microbial profiles of saliva and fecal samples were distinct. Mycoplasma faucium, Tannerella forsythia, Parvimonas micra, and Saccharibacteria (TM7) were increased in P; Prevotella pallens, Prevotella melaninogenica, Neisseria multispecies were more abundant in PA+P group, Ruthenibacterium lactatiformans, Dialister succinatiphilus, Butyrivibrio crossotus and Alloprevotella tannerae were detected in fecal samples in P groups compared to healthy controls. Conclusions: No significant differences were detected between Parkinson's and non-Parkinson's gut microbiomes, suggesting that Parkinson's disease modifies the oral microbiome in periodontitis subjects independent of the gut microbiome.

Clinical and Treatment History of Patients with Partial DiGeorge Syndrome and Autoimmune Cytopenia at Multiple Centers.

BACKGROUND: Patients with partial DiGeorge syndrome (pDGS) can present with immune dysregulation, the most common being autoimmune cytopenia (AIC). There is a lack of consensus on the approach to type, combination, and timing of therapies for AIC in pDGS. Recognition of immune dysregulation early in pDGS clinical course may help individualize treatment and prevent adverse outcomes from chronic immune dysregulation. OBJECTIVES: Objectives of this study were to characterize the natural history, immune phenotype, and biomarkers in pDGS with AIC. METHODS: Data on clinical presentation, disease severity, immunological phenotype, treatment selection, and response for patients with pDGS with AIC were collected via retrospective chart review. Flow cytometric analysis was done to assess T and B cell subsets, including biomarkers of immune dysregulation. RESULTS: Twenty-nine patients with the diagnosis of pDGS and AIC were identified from 5 international institutions. Nineteen (62%) patients developed Evan's syndrome (ES) during their clinical course and twenty (69%) had antibody deficiency syndrome. These patients demonstrated expansion in T follicular helper cells, CD19hiCD21lo B cells, and double negative cells and reduction in CD4 naïve T cells and regulatory T cells. First-line treatment for 17/29 (59%) included corticosteroids and/or high-dose immunoglobulin replacement therapy. Other overlapping therapies included eltrombopag, rituximab, and T cell immunomodulators. CONCLUSIONS: AIC in pDGS is often refractory to conventional AIC treatment paradigms. Biomarkers may have utility for correlation with disease state and potentially even response to therapy. Immunomodulating therapies could be initiated early based on early immune phenotyping and biomarkers before the disease develops or significantly worsens.

Occurrence of radiopaque and mixed lesions at periapical region in patients with rheumatoid arthritis and ankylosing spondylitis: a retrospective study.

BACKGROUND: Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) have different effects on bones, cartilage and joints, sometimes destroying the spine and joints, and other times causing new bone formation. This study aimed to evaluate the effects of RA and AS on the types (radiolucent, radiopaque and mixed) of periapical lesions in jaw bones. METHODS: This study included 708 individuals (97 with AS, 327 with RA and 284 healthy controls (C)) and a total of 17,118 teeth (AS: 2,442; RA: 7,638; C: 7,038). The number of teeth, extracted teeth and teeth with root canal treatment and the presence of radiopaque, radiolucent and mixed periapical lesions were recorded from dental panoramic radiographs. Kruskal-Wallis and chi-square tests were used for statistical analysis. RESULTS: The frequency of radiopaque lesions in the AS and RA groups was similar (p > 0.05) and significantly higher than in the C group (p < 0.05) (AS: 13.4%; RA: 6.1%; C: 2%). Mixed lesions (AS: 3.1%; RA: 4.0%; C: 0.4%) were statistically significantly higher for the RA group compared to the C group (p < 0.05), while the AS-C and AS-RA groups were similar (p > 0.05). There was no significant difference in terms of radiolucent lesions among groups (p > 0.05). CONCLUSION: Radiopaque apical lesions were frequent in RA and AS patients, while mixed lesions were significantly higher in RA patients.

Parkinson's disease alters the composition of subgingival microbiome.

Aim: The current study aimed to test the hypothesis that Parkinson's disease exacerbates periodontitis by altering its microbiome. Materials and Methods: Clinical periodontal parameters were recorded. Subgingival samples from healthy controls, periodontitis patients (PD), and Parkinson's patients with periodontitis (PA+PD) were analyzed using the checkerboard DNA-DNA hybridization technique for targeting 40 bacterial species typically associated with periodontal disease and health. Next-generation sequencing (NGS) of the 16S ribosomal RNA gene (V1-V3 regions) was performed to analyze the microbiome comprehensively. Results: Parkinson's patients had mild-to-moderate motor dysfunctions. Bleeding on probing was significantly increased in the PA+PD group compared to PD (p < 0.05). With checkerboard analysis, PA was associated with increased Treponema socranskii (p = 0.0062), Peptostreptococcaceae_[G-6] [Eubacterium]_nodatum (p = 0.0439), Parvimona micra (p < 0.0001), Prevotella melaninogenica (p = 0.0002), Lachnoanaerobaculum saburreum (p < 0.0001), and Streptococcus anginosus (p = 0.0020). Streptococcus intermedia (p = 0.0042), P.nodatum (p = 0.0022), P. micra (p = 0.0002), Treponema denticola (p = 0.0045), L.saburreum (p = 0.0267), P.melaninogenica (p = 0.0017), Campylobacter rectus (p = 0.0020), and T.socranskii (p = 0.0002) were higher; Aggregatibacter actinomycetemcomitans (p = 0.0072) was lower in deep pockets in the PA+PD compared to PD. Schaalia odontolytica (p = 0.0351) and A.actinomycetemcomitans (p = 0.002) were lower; C.rectus (p = 0.0002), P. micra (p = 0065), Streptococcus constellatus (p = 0.0151), T.denticola (p = 0.0141), P.melaninogenica (p = 0.0057), and T.socranskii (p = 0.0316) were higher in shallow pockets in the PA+PD. Diversity decreased in PD (p = 0.001) and PA+PD (p = 0.026) compared to control, with minimal differences in alpha and beta diversities among PD and PA+PD based on NGS results. Conclusion: These data demonstrated that Parkinson's disease modifies PD-associated subgingival microbiome.

A comparison of online and face-to-face modalities in endodontic preclinical education: A retrospective study.

PURPOSE: The aim of this study was to evaluate the competency of undergraduate students in following the principles of access cavity preparation and the radiographic quality of root canal filling in maxillary molar teeth in either online or face-to-face education courses during the novel coronavirus disease 2019 (COVID-19) pandemic. METHODS: A total of 178 extracted maxillary molar teeth that underwent endodontic dental treatment by undergraduate students who completed the endodontic preclinical practice course online or face-to-face during the COVID-19 pandemic were retrospectively analyzed. A visual access cavity examination determined the form, width of the cavity, deroofing of the pulp chamber, and the presence of a perforation. Root canal fillings were examined radiographically on periapical radiographs for length, homogeneity, taper, and the presence of iatrogenic defects. Statistical analysis was performed using the chi-square test. RESULTS: The incidence of incorrect form, wide cavities, and perforation was statistically higher in the online group than in the face-to-face group (p < 0.05). It was determined that root filling length and homogeneity were more successful in the face-to-face group (p < 0.05). When evaluated for iatrogenic errors, the presence of broken instruments was found to be significantly higher in the online group (p < 0.05). There was no significant difference between the groups in other iatrogenic errors and the taper of the root canal filling (p > 0.05). CONCLUSION: The students who underwent face-to-face education were more successful in accessing cavity preparation and root canal fillings than the students who undertook online education.

Evaluation of the effect of sickle cell disease on the mandibular bone of children and adolescents by image texture and radiomorphometric analysis.

OBJECTIVES: Sickle cell disease (SCD) can cause osteoporotic changes in the jaw bones. In this study, it was aimed to evaluate possible bone changes using fractal analysis (FA) and morphometric analyses in dental panoramic radiographs of children and adolescents diagnosed with both homozygous and heterozygous forms of SCD. METHODS: Sixty-five individuals (33 SCD, 32 controls) aged 6-17 years were included in the study. Four separate areas of interest (ROI) were selected for the right and left sides of all panoramic radiographs, and the FA value of the ROIs was calculated. Mandibular cortical width (MCW), panoramic mandibular index (PMI) and mandibular cortical index (MCI) and were evaluated. Data were statistically analyzed and p < 0.05 was accepted for statistical significance. RESULTS: Fractal values of right and left ROI1 (the center of the mandibular angle.) and ROI4 (the cortical bone), and right ROI2 (the middle of the mandibular ramus) were statistically lower in the case group (p < 0.05). Right ROI2 and ROI4 fractal values of individuals in the case group were lower than those on the left side (p < 0.05). While MCI categories did not differ from the case-control group (p > 0.05), PMI and MCW values were lower in the case group (p < 0.05). All evaluated parameters did not differ according to age and gender (p > 0.05). CONCLUSION: The results of this study showed that SCD affects the mandible. FA, MCW and PMI parameters can be used to detect early osteoporotic changes in the disease.

Parkinson's disease is positively associated with periodontal inflammation.

BACKGROUND: Parkinson's disease (PA) affects 1% of the global population above 60 years. PA pathogenesis involves severe neuroinflammation that impacts systemic and local inflammatory changes. We tested the hypothesis that PA is associated with periodontal tissue inflammation promoting a greater systemic inflammatory burden. METHODS: We recruited 60 patients with Stage III, Grade B periodontitis (P) with and without PA (n = 20 for each). We also included systemically and periodontally healthy individuals as controls (n = 20). Clinical periodontal parameters were recorded. Serum, saliva, and gingival crevicular fluid (GCF) samples were collected to measure the inflammatory and neurodegenerative targets (YKL-40, fractalkine, S100B, alpha-synuclein, tau, vascular cell adhesion protein-1 (VCAM-1), brain-derived neurotrophic factor (BDNF), neurofilament light chain (NfL). RESULTS: Parkinson's patients in this study had mild to moderate motor dysfunctions, which did not prevent them from performing optimal oral hygiene control. Periodontal parameters and GCF volume were significantly higher in the P and P+PA groups than in the control group. PA was associated with significantly increased bleeding on probing (BOP) compared to P-alone (p < 0.05), while other clinical parameters were similar between P and P+PA groups. In saliva and serum, YKL-40 levels were higher in the P+PA group than in P and C groups (p < 0.001). GCF NfL levels from shallow sites were significantly higher in the P+PA group compared to the C group (p = 0.0462). GCF S100B levels from deep sites were higher in the P+PA group than in healthy individuals (p = 0.0194). CONCLUSION: The data suggested that PA is highly associated with increased periodontal inflammatory burden-bleeding upon probing and inflammatory markers-in parallel with PA-related neuroinflammation.

Do arginine metabolites have a role in periodontitis due to smoking? A new perspective.

OBJECTIVES: Cigarette consumption is common around the world and besides its negative effects on health, and its effects on periodontitis draw attention. Arginine metabolites are involved in the pathogenesis of several systemic inflammatory diseases' including cardiovascular diseases. Our aim was to determine periodontitis and healthy individuals' arginine metabolites and IL-6 levels in saliva and serum and to evaluate those according to smoking status. MATERIALS AND METHODS: The study consisted of four groups: healthy individuals (control [C]; n = 20), smokers with healthy periodontium (S-C; n = 20), nonsmokers with Stage-III Grade-B generalized periodontitis (P; n = 20) and smokers with Stage-III Grade-C generalized periodontitis (S-P; n = 18). Periodontal parameters were measured. Analysis of methylated arginine metabolites was performed by LC-MS/MS, and IL-6 levels were determined by ELISA kits. RESULTS: In nonsmokers, salivary concentrations of asymmetric dimethylarginine (ADMA) and symmetrical dimethylarginine (SDMA) were higher in the periodontitis than control (p < 0.001, p = 0.010). Smokers with periodontitis exhibited higher ADMA (p = 0.033, p < 0.001) and arginine (p = 0.030, p = 0.001) saliva concentrations than smoking and nonsmoking controls. CONCLUSIONS: Our results demonstrated that salivary concentrations of ADMA and SDMA were associated with periodontitis. Smoking increased ADMA, SDMA and NG -monomethyl L-arginine (L-NMMA) levels in serum only in periodontitis patients.

Can we identify WHIM in infancy? Opportunities with the public newborn screening process.

Newborn screening (NBS) for severe combined immunodeficiency (SCID) utilizing T-cell receptor excision circles (TRECs) has been implemented in all 50 states as of December 2018 and has been transformative for the clinical care of SCID patients. Though having high sensitivity for SCID, NBS-SCID has low specificity, therefore is able to detect other causes of lymphopenia in newborns including many inborn errors of immunity (IEIs). In a recent study, three of six newborns later diagnosed with Warts, Hypogammaglobulinemia, Infections, and Myelokathexis (WHIM) syndrome were found to have a low TRECs and lymphopenia at birth. This presents an opportunity to increase the detection and diagnosis of WHIM syndrome by NBS-SCID with immunological follow-up along with a combination of flow cytometry for immune cell subsets, absolute neutrophil count, and genetic testing, extending beyond the conventional bone marrow studies. Coupled with emerging technologies such as next-generation sequencing, transcriptomics and proteomics, dried blood spots used in NBS-SCID will promote earlier detection, diagnosis, and therefore treatment of IEIs such as WHIM syndrome.

Disease Progression of WHIM Syndrome in an International Cohort of 66 Pediatric and Adult Patients.

Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome (WS) is a combined immunodeficiency caused by gain-of-function mutations in the C-X-C chemokine receptor type 4 (CXCR4) gene. We characterize a unique international cohort of 66 patients, including 57 (86%) cases previously unreported, with variable clinical phenotypes. Of 17 distinct CXCR4 genetic variants within our cohort, 11 were novel pathogenic variants affecting 15 individuals (23%). All variants affect the same CXCR4 region and impair CXCR4 internalization resulting in hyperactive signaling. The median age of diagnosis in our cohort (5.5 years) indicates WHIM syndrome can commonly present in childhood, although some patients are not diagnosed until adulthood. The prevalence and mean age of recognition and/or onset of clinical manifestations within our cohort were infections 88%/1.6 years, neutropenia 98%/3.8 years, lymphopenia 88%/5.0 years, and warts 40%/12.1 years. However, we report greater prevalence and variety of autoimmune complications of WHIM syndrome (21.2%) than reported previously. Patients with versus without family history of WHIM syndrome were diagnosed earlier (22%, average age 1.3 years versus 78%, average age 5 years, respectively). Patients with a family history of WHIM syndrome also received earlier treatment, experienced less hospitalization, and had less end-organ damage. This observation reinforces previous reports that early treatment for WHIM syndrome improves outcomes. Only one patient died; death was attributed to complications of hematopoietic stem cell transplantation. The variable expressivity of WHIM syndrome in pediatric patients delays their diagnosis and therapy. Early-onset bacterial infections with severe neutropenia and/or lymphopenia should prompt genetic testing for WHIM syndrome, even in the absence of warts.

Topical Sevoflurane: A Novel Treatment for Chronic Pain Caused by Venous Stasis Ulcers.

In the US, an estimated 1 - 2% of chronic venous insufficiency (CVI) patients (of 6 - 7 million nationwide) develop at least one venous stasis ulcer (VSU) during their illness. Of these, approximately 40% develop subsequent ulcers, making VSU prognostically poor. Current management of VSU is costly, with poor prognosis, high recurrence rate, inadequate pain management, and significantly reduced quality of life (QoL). Topical volatile anesthetic agents, such as sevoflurane, offer improved pain relief and symptom control in patients suffering from chronic VSU. The immediate impact of topical sevoflurane in reducing pain associated with ulcer bed debridement has several implications in improving the quality of life in patients with CVI induced ulcers and in the prognosis and healing of the ulcers. This review summarizes a topical formulation of a volatile anesthetic and its implications for the management of VSUs.

Overexpression of schizophrenia susceptibility factor human complement C4A promotes excessive synaptic loss and behavioral changes in mice.

The complement component 4 (C4) gene is linked to schizophrenia and synaptic refinement. In humans, greater expression of C4A in the brain is associated with an increased risk of schizophrenia. To investigate this genetic finding and address how C4A shapes brain circuits in vivo, here, we generated a mouse model with primate-lineage-specific isoforms of C4, human C4A and/or C4B. Human C4A bound synapses more efficiently than C4B. C4A (but not C4B) rescued the visual system synaptic refinement deficits of C4 knockout mice. Intriguingly, mice without C4 had normal numbers of cortical synapses, which suggests that complement is not required for normal developmental synaptic pruning. However, overexpressing C4A in mice reduced cortical synapse density, increased microglial engulfment of synapses and altered mouse behavior. These results suggest that increased C4A-mediated synaptic elimination results in abnormal brain circuits and behavior. Understanding pathological overpruning mechanisms has important therapeutic implications in disease conditions such as schizophrenia.

An Evidence-Based Review of Galcanezumab for the Treatment of Migraine.

PURPOSE OF REVIEW: This is a comprehensive review of the current literature on the usage of galcanezumab for migraine treatment. It reviews the biology, pathophysiology, epidemiology, diagnosis, and conventional treatment of migraines, then compares the literature available for galcanezumab with historical treatment options. RECENT FINDINGS: Migraine is a common headache disorder and constitutes a significant source of distress from both a personal and societal perspective. Conventional treatment includes abortive and preventive treatment. Treatment options are limited and may be only partially or minimally effective in some of the population. Recent evidence points to metabolic changes in the brain as possible causes of migraine, via reduced available energy or a spiking need for it, resulting in a relative insufficiency. This leads to trigeminocervical complex (TCC) activation and a headache episode, modulated by calcitonin gene-related peptide (CGRP). Galcanezumab (Emgality) is a monoclonal antibody targeting CGRP that is given in a monthly injection for the prevention of migraines. Its safety was previously shown in phase 1 and 2 trials, and recent phase 3 trials showed efficacy, with up to 50% reduction in monthly migraine days and improved functional capacity in migraineurs. Studies show that the drug is well tolerated and safe. Migraine headache is a common neurological syndrome that causes great pain and suffering. Treatment options today are limited. Galcanezumab does not prevent migraines, but it is effective in decreasing their frequency and length. It is also much better tolerated than the currently existing therapies. While it is unlikely to provide monotherapy for migraines, it is a novel therapy that may be added for cases of severe or frequent migraines.

Utilization of B12 for the treatment of chronic migraine.

Chronic migraine is a particular classification of a headache that is typically unilateral and pulsatile and lasts for at least 3 months. Owing to its high prevalence and detrimental impact on personal, social, and economic aspects of patient lives, much desire has gone into fully understanding the pathogenesis of migraine, and to search for therapeutic agents. In addition to current therapeutics such as triptans, ergotamine, and monoclonal antibodies targeting calcitonin gene-related peptide receptors, vitamin B12 has been investigated for its possible use as a prophylactic agent for migraines. Specifically, the observed effects of vitamin B12 on nitric oxide and homocysteine prompt further investigation of its underlying mechanisms in migraine pathophysiology. In this comprehensive review, we provide a brief overview of migraines and current therapies while focusing on the promising role of vitamin B12 as a possible treatment option for chronic migraine management.

Postherpetic Neuralgia: Current Evidence on the Topical Film-Forming Spray with Bupivacaine Hydrochloride and a Review of Available Treatment Strategies.

PURPOSE OF REVIEW: This is a comprehensive review of the literature about the use of bupivacaine hydrochloride for the treatment of post-herpetic neuralgia (PHN). It briefly reviews the background, biology, diagnosis and conventional treatment for PHN, and then introduces and compares the recent evidence for the use of topical bupivacaine. RECENT FINDINGS: PHN is defined by pain lasting 90 days or more after the initial presentation of herpes zoster ("Shingles", HZ) rash and is the most common complication of this disease. A product of re-activation of the Varicella-Zoster virus (VZV), HZ is diagnosed more than 1 million times annually in the United States. Approximately 20% of patients with HZ will experience PHN and will continue to suffer intermittent neuropathic symptoms, including itching and pain, that is sharp, stabbing, throbbing or burning, with the pain localized to the site of their original rash. This long-lasting pain compares with the severity of long-standing rheumatics and osteo-arthritis and is accompanied by severe allodynia causing significant suffering, and a financial burden that is manifested in both healthcare costs and loss of quality-adjusted life years. Prevention of PHN may be achieved with the Zoster vaccine, although there is still a large segment of unvaccinated population. Moreover, the Zoster vaccine is not always effective for prevention. Current treatment includes medical (systemic tricyclic antidepressants, anticonvulsants and opioids, topical lidocaine and capsaicin) and interventional (subcutaneous Botox injections, nerve blocks and nerve stimulation) therapies. These therapies are not always effective, and each carries their own profile of side effects and risks. Moreover, up to 50% of patients with PHN are refractory to management. Recent evidence is emerging to support the use of topical local anesthetics for the treatment of PHN. Two small studies recently found topical lidocaine spray to be effective in treating paroxysmal pain attacks associated with PHN. Bupivacaine is a longer-lasting local anesthetic, and a film-forming formulation allows easy and durable application to the affected skin. Recent studies show that topical film-forming bupivacaine is safe and as effective as lidocaine for the treatment of PHN. PHN is an important though common complication of HZ and can cause long-lasting pain and disability. Current treatment for PNH is limited by efficacy and safety profiles of individual therapies. Recent evidence points to topical local anesthetics as an effective and safe alternative to conventional therapy. Film-forming bupivacaine may offer a durable and safe option for this otherwise difficult to treat syndrome.

Immune-Related Adverse Events (irAEs): Diagnosis, Management, and Clinical Pearls.

PURPOSE OF REVIEW: While immune checkpoint inhibitor (ICI) therapy has improved melanoma patient outcomes, it has also resulted in the rise of unique immune-related adverse events (irAEs). Here, we review and synthesize irAE management recommendations from several oncological societies into a streamlined format to aid in diagnosis and management. We also include clinical pearls highlighting several recent research studies in this field. RECENT FINDINGS: Knowledge of immunotherapy toxicity has continually evolved, and several major oncologic societies have recently released new or updated guidelines. Keeping up with the evolving field of immunotherapy and related toxicities is crucial, because ICI use, in combination with other agents, will only continue to increase and likely result in new and different patterns of irAEs. Providing clear and concise references for clinicians will help ensure proper irAE evaluation and management going forward. We present one such reference here, covering management of common and/or serious irAEs.

Fear: It's All in Your Line of Sight.

The brain circuits that create our sense of fear rely on ancient 'hard-wired' components of the limbic system, but also use sensory processing to determine what we become afraid of. A new study shows that, when viewing of simple oriented line stimuli is coupled with aversive experiences, neurons in primary visual cortex rapidly alter their responses in a manner that indicates the line stimuli become a source of fear.

High-Impact Mechanical Loading Increases Bone Material Strength in Postmenopausal Women-A 3-Month Intervention Study.

Bone adapts to loading in several ways, including redistributing bone mass and altered geometry and microarchitecture. Because of previous methodological limitations, it is not known how the bone material strength is affected by mechanical loading in humans. The aim of this study was to investigate the effect of a 3-month unilateral high-impact exercise program on bone material properties and microarchitecture in healthy postmenopausal women. A total of 20 healthy and inactive postmenopausal women (aged 55.6 ± 2.3 years [mean ± SD]) were included and asked to perform an exercise program of daily one-legged jumps (with incremental number, from 3×10 to 4×20 jumps/d) during 3 months. All participants were asked to register their performed jumps in a structured daily diary. The participants chose one leg as the intervention leg and the other leg was used as control. The operators were blinded to the participant's choice of leg for intervention. The predefined primary outcome was change in bone material strength index (BMSi), measured at the mid tibia with a handheld reference probe indentation instrument (OsteoProbe). Bone microstructure, geometry, and density were measured with high-resolution peripheral quantitative computed tomography (XtremeCT) at the ultradistal and at 14% of the tibia bone length (distal). Differences were analyzed by related samples Wilcoxon signed rank test. The overall compliance to the jumping program was 93.6%. Relative to the control leg, BMSi of the intervention leg increased 7% or 0.89 SD (p = 0.046), but no differences were found for any of the XtremeCT-derived bone parameters. In conclusion, a unilateral high-impact loading program increased BMSi in postmenopausal women rapidly without affecting bone microstructure, geometry, or density, indicating that intense mechanical loading has the ability to rapidly improve bone material properties before changes in bone mass or structure. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.