Alterations in compositional and cellular properties of the subchondral bone are linked to cartilage degeneration in hip osteoarthritis.

OBJECTIVE: The subchondral bone is an emerging regulator of osteoarthritis (OA). However, knowledge of how specific subchondral alterations relate to cartilage degeneration remains incomplete. METHOD: Femoral heads were obtained from 44 patients with primary OA during total hip arthroplasty and from 30 non-OA controls during autopsy. A multiscale assessment of the central subchondral bone region comprising histomorphometry, quantitative backscattered electron imaging, nanoindentation, and osteocyte lacunocanalicular network characterization was employed. RESULTS: In hip OA, thickening of the subchondral bone coincided with a higher number of osteoblasts (controls: 3.7 ± 4.5 mm-1, OA: 16.4 ± 10.2 mm-1, age-adjusted mean difference 10.5 mm-1 [95% CI 4.7 to 16.4], p < 0.001) but a similar number of osteoclasts compared to controls (p = 0.150). Furthermore, higher matrix mineralization heterogeneity (CaWidth, controls: 2.8 ± 0.2 wt%, OA: 3.1 ± 0.3 wt%, age-adjusted mean difference 0.2 wt% [95% CI 0.1 to 0.4], p = 0.011) and lower tissue hardness (controls: 0.69 ± 0.06 GPa, OA: 0.67 ± 0.06 GPa, age-adjusted mean difference -0.05 GPa [95% CI -0.09 to -0.01], p = 0.032) were detected. While no evidence of altered osteocytic perilacunar/canalicular remodeling in terms of fewer osteocyte canaliculi was found in OA, specimens with advanced cartilage degeneration showed a higher number of osteocyte canaliculi and larger lacunocanalicular network area compared to those with low-grade cartilage degeneration. Multiple linear regression models indicated that several subchondral bone properties, especially osteoblast and osteocyte parameters, were closely related to cartilage degeneration (R2 adjusted = 0.561, p < 0.001). CONCLUSION: Subchondral bone properties in OA are affected at the compositional, mechanical, and cellular levels. Based on their strong interaction with cartilage degeneration, targeting osteoblasts/osteocytes may be a promising therapeutic OA approach. DATA AND MATERIALS AVAILABILITY: All data are available in the main text or the supplementary materials.

Access disparities and underutilization of germline genetic testing in Chilean breast cancer patients.

PURPOSE: Latin American reports on genetic cancer risk assessments are scarce. In Chile, current breast cancer (BC) guidelines do not define strategies for germline genetic testing. Our study sought to quantify the disparities in access to genetic testing in Chilean BC patients, according to international standards and their clinical characteristics to explore improvement strategies. METHODS: Retrospective analysis of invasive BC databases including patients treated in a Public Hospital (PH) and in an Academic Private Center (AC) in Santiago, Chile between 2012 and 2021. RESULTS: Of 5438 BC patients, 3955 had enough data for National Comprehensive Cancer Network (NCCN) categorization. From these, 1911 (48.3%) fulfilled NCCN criteria for germline testing, of whom, 300 were tested for germline mutations and 268 with multigene panels. A total of 65 pathogenic variants were found in this subset. As expected, BRCA1/2 mutations were the most frequent (17.7%). Access to genetic testing was higher in AC versus PH (19.6% vs. 10.3%, p = 0.0001). Other variables associated with germline genetic testing were BC diagnosis after 2018, being 45 years old or younger at diagnosis, BC family history (FH), FH of ovarian cancer, non-metastatic disease, and triple-negative subtype. CONCLUSION: In our cohort, 15% of BC patients who met NCCN criteria for germline testing were effectively tested. This percentage was even lower at the PH. Current recommendations encourage universal genetic testing for BC patients; however, our findings suggest that Chile is far from reaching such a goal and national guidelines in this regard are urgently needed. To our knowledge, this is the first study of its kind in Chile and Latin America.

Reduced cement volume does not affect screw stability in augmented pedicle screws.

PURPOSE: Cement augmentation of pedicle screws is able to improve screw anchorage in osteoporotic vertebrae but is associated with a high complication rate. The goal of this study was to evaluate the impact of different cement volumes on pedicle screw fatigue strength. METHODS: Twenty-five human vertebral bodies (T12-L4) were collected from donors between 73 and 97 years of age. Bone density (BMD) was determined by quantitative computed tomography. Vertebral bodies were instrumented by conventional pedicle screws, and unilateral cement augmentation was performed. Thirteen vertebrae were augmented with a volume of 1 ml and twelve with a volume of 3 ml bone cement. A fatigue test was performed using a cranial-caudal sinusoidal, cyclic load (0.5 Hz) with increasing compression force (100 N + 0.1 N/cycles). RESULTS: The load to failure was 183.8 N for the non-augmented screws and was increased significantly to 268.1 N (p < 0.001) by cement augmentation. Augmentation with 1 ml bone cement increased the fatigue load by 41% while augmentation with 3 ml increased the failure load by 51% compared to the non-augmented screws, but there was no significant difference in fatigue loads between the specimens with screws augmented with 1 ml and screws augmented with 3 ml of bone cement (p = 0.504). CONCLUSION: Cement augmentation significantly increases pedicle screw stability. The benefit of augmentation on screw anchorage was not significantly affected by reducing the applied volume of cement from 3 ml to 1 ml. Considering the high risk of cement leakage during augmentation, we recommend the usage of a reduced volume of 1 ml bone cement for each pedicle screw. These slides can be retrieved under Electronic Supplementary Material .

Time to augment?! Impact of cement augmentation on pedicle screw fixation strength depending on bone mineral density.

PURPOSE: Cement augmentation of pedicle screws is known to increase their mechanical strength. Aim was to evaluate the impact of cement augmentation on pedicle screw fatigue strength in dependence of the bone mineral density (BMD). METHODS: Twenty-one human L2 vertebral bodies from donors between 19 and 96 years of age were used for in vitro experiments. BMD was measured using quantitative computed tomography (QCT). Two pedicle screws were inserted in each specimen and unilaterally augmented with bone cement. Fatigue testing was performed using a cranio-caudal sinusoidal, cyclic load (0.5 Hz) with increasing compression force (100 N + 0.1 N/cycles). Results were evaluated for the BMD groups: normal: BMD > 120 mg/cm3, osteopenic: BMD 80-120 mg/cm3, and osteoporotic: BMD < 80 mg/cm3 bone mass. RESULTS: There was a significant correlation between fatigue force and BMD for the non-augmented and augmented screws (non-augmented R2 = 0.839, p < 0.001; augmented R2 = 0.551, p < 0.001). There was a significantly increased fatigue strength of the augmented screws over the non-augmented screws in the osteoporotic group (p = 0.001), while the differences in the other groups were not significant (normal p = 0.818/osteopenic p = 0.132). CONCLUSIONS: The benefit of pedicle screw cement augmentation significantly depends on the bone mineral density and has the greatest extent of increased fatigue strength in osteoporotic vertebrae. Preoperative measurement of the BMD is strongly recommended to predict the benefit of augmentation and reinforce the decision for cement augmentation. These slides can be retrieved under Electronic Supplementary Material.

Differential Intracochlear Sound Pressure Measurements in Human Temporal Bones with an Off-the-Shelf Sensor.

The standard method to determine the output level of acoustic and mechanical stimulation to the inner ear is measurement of vibration response of the stapes in human cadaveric temporal bones (TBs) by laser Doppler vibrometry. However, this method is reliable only if the intact ossicular chain is stimulated. For other stimulation modes an alternative method is needed. The differential intracochlear sound pressure between scala vestibuli (SV) and scala tympani (ST) is assumed to correlate with excitation. Using a custom-made pressure sensor it has been successfully measured and used to determine the output level of acoustic and mechanical stimulation. To make this method generally accessible, an off-the-shelf pressure sensor (Samba Preclin 420 LP, Samba Sensors) was tested here for intracochlear sound pressure measurements. During acoustic stimulation, intracochlear sound pressures were simultaneously measurable in SV and ST between 0.1 and 8 kHz with sufficient signal-to-noise ratios with this sensor. The pressure differences were comparable to results obtained with custom-made sensors. Our results demonstrated that the pressure sensor Samba Preclin 420 LP is usable for measurements of intracochlear sound pressures in SV and ST and for the determination of differential intracochlear sound pressures.

Mammogram screening in Chile: using mixed methods to implement health policy planning at the primary care level.

Breast cancer has the highest incidence of all cancers among women in Chile. In 2005, a national health program progressively introduced free mammography screening for women aged 50 and older; however, three years later the rates of compliance with mammographic screening was only 12% in Santiago, the capital city of Chile. This implementation article combines the findings of two previous studies that applied qualitative and quantitative methods to improve mammography screening in an area of Santiago. Socio-cultural and accessibility factors were identified as barriers and facilitators during the qualitative phase of the study and then applied to the design of a quantitative randomized clinical trial. After six months of intervention, 6% of women in the standard care group, 51.8% in the low intensity intervention group, and 70.1% in the high intensity intervention group had undergone a screening mammogram. This review discusses how the utilization of mixed methods research can contribute to the improvement of the implementation of health policies in local communities.

Skeletal analysis and comparison of bog bodies from Northern European peat bogs.

Although numerous bodies were deposited in Western European bogs in the past centuries, few were found and underwent archeological analysis. No studies comparing skeletal structure and mineralization of bog bodies from different ages have been performed to this day. Therefore, the aim of this study was to analyze and compare skeletal features and specifics of the human remains of three bog bodies from the Iron and Middle Ages found in Northern European peat bogs. Demineralization due to the acidic environment in peat bogs was comparably pronounced in all three bodies. Still, the macroscopic state of skeletal preservation was excellent. In addition to contact radiography, we used peripheral quantitative computed tomography to measure cortical bone mineral density. The conservation of skeletal three-dimensional microstructural elements was assessed by high-resolution microcomputed tomography analysis. These techniques revealed severe differences in bone mineral density and enabled us to determine handedness in all three bodies. Additionally, unique skeletal features like intravital bone lesions, immobilization osteoporosis, and Harris lines were found. A deformity of the left femoral head was observed which had the typical appearance of an advanced stage of Legg-Calve-Perthes disease. This study gives detailed insight into the skeletal microstructure and microarchitecture of 800- to 2,700-year-old bog bodies. Skeletal analysis enables us to draw conclusions not only concerning changes in the acidic environment of the bog, but also serves as a diagnostic tool to unravel life circumstances and diseases suffered by humans in the Iron and Middle Ages.

Bone mineralization defects and vitamin D deficiency: histomorphometric analysis of iliac crest bone biopsies and circulating 25-hydroxyvitamin D in 675 patients.

Parathyroid hormone (PTH) is only one measurable index of skeletal health, and we reasoned that a histomorphometric analysis of iliac crest biopsies would be another and even more direct approach to assess bone health and address the required minimum 25-Hydroxyvitamin D [25(OH)D] level. A cohort from the northern European population with its known high prevalence of vitamin D deficiency therefore would be ideal to answer the latter question. We examined 675 iliac crest biopsies from male and female individuals, excluding all patients who showed any signs of secondary bone diseases at autopsy. Structural histomorphometric parameters, including osteoid indices, were quantified using the Osteomeasure System according to ASBMR standards, and serum 25(OH)D levels were measured for all patients. Statistical analysis was performed by Student's t test. The histologic results demonstrate an unexpected high prevalence of mineralization defects, that is, a pathologic increase in osteoid. Indeed, 36.15% of the analyzed patients presented with an osteoid surface per bone surface (OS/BS) of more than 20%. Based on the most conservative threshold that defines osteomalacia at the histomorphometric level with a pathologic increase in osteoid volume per bone volume (OV/BV) greater than 2% manifest mineralization defects were present in 25.63% of the patients. The latter were found independent of bone volume per trabecular volume (BV/TV) throughout all ages and affected both sexes equally. While we could not establish a minimum 25(OH)D level that was inevitably associated with mineralization defects, we did not find pathologic accumulation of osteoid in any patient with circulating 25(OH)D above 75 nmol/L. Our data demonstrate that pathologic mineralization defects of bone occur in patients with a serum 25(OH)D below 75 nmol/L and strongly argue that in conjunction with a sufficient calcium intake, the dose of vitamin D supplementation should ensure that circulating levels of 25(OH)D reach this minimum threshold (75 nmol/L or 30 ng/mL) to maintain skeletal health.