Purpose. To evaluate the effect of teriparatide (TPTD) on bone mineral density (BMD) and bone mar... more Purpose. To evaluate the effect of teriparatide (TPTD) on bone mineral density (BMD) and bone markers under clinical practice conditions. To assess whether the results in real-life match those published in clinical trials. Methods. Cross-sectional study of postmenopausal women treated with TPTD for at least 12 months. Results. 264 patients were included in the study. Main characteristics are as follows: age: 68.7 ± 10.2 years, previous fractures: 57.6%, and previously treated with antiresorptive (AR-prior): 79%. All bone turnover markers studied significantly increased after 6 months. CTX and BGP remained high up to 24 months, but total and bone alkaline phosphatase returned to basal values at month 18. There was a significant increase in lumbar spine (LS) BMD after 6 months (+6.2%), with a maximum peak at 24 months (+13%). Femoral neck (FN) and total hip (TH) BMD showed a significant increase later than LS (just at month 12), reaching a maximum peak at month 24 (FN + 7.9% and TH + ...
Heterotopic ossification (HO) is the formation of extraskeletal bone in muscle and soft tissues a... more Heterotopic ossification (HO) is the formation of extraskeletal bone in muscle and soft tissues and could be genetic or non-genetic. The classic presentation of non-genetic HO is in young adults with a clear history of local trauma, surgery or prolonged immobilization after spinal cord and traumatic brain injuries. Genetic HO has a significant clinical severity compared to non-genetic causes and includes fibrodysplasia ossificans progressiva (FOP). FOP is an extremely rare genetic skeletal disorder characterized by congenital malformations of the great toes and progressive heterotopic ossification that forms qualitatively normal bone in characteristic extraskeletal sites affecting skeletal muscles, fascia, tendons, and ligaments. Previously, it has been reported an association between SARS-CoV-2 infection (COVID-19) and HO or FOP exacerbation with unclear etiopathogenesis. The possible mechanisms could be prolonged immobilization and systemic inflammation. Here, we describe the case of a 55-year-old apparently healthy man who suffered from a severe SARS-CoV-2 infection after that he experienced an extensive and progressive heterotopic ossification around the shoulders, the elbows, the hip, the knees, and the ankles. Because of the clinical severity, the painful soft-tissue swelling, the progressive HO, and the bilateral congenital hallux valgus deformity, a late-onset atypical FOP was suspected. Nevertheless, no variant of clinical significance has been identified in the coding regions and splicing sites in the ACVR1 gene and no deletions and/or duplications have been identified in exonic regions.
Existe la creencia popular que el consumo habitual de yerba mate (YM) provoca acidez o gastritis.... more Existe la creencia popular que el consumo habitual de yerba mate (YM) provoca acidez o gastritis. De hecho, en internet aparece gran cantidad de informacion sobre ello y multiples recomendaciones medicas. Sin embargo, la evidencia cientifica al respecto es pobre.
El consumo de yerba mate (Ilex paraguariensis) es muy frecuente en varios paises de America Latin... more El consumo de yerba mate (Ilex paraguariensis) es muy frecuente en varios paises de America Latina. Varios fitoquimicos activos como xantinas (cafeina) y polifenoles (acido clorogenico, quercetina, rutina) han sido identificados en extractos acuosos de Ilex paraguariensis. Entre los componentes de la yerba mate con efecto sobre el tejido oseo se destaca que la cafeina en altas concentraciones tendria un impacto negativo sobre la densidad mineral osea (DMO) sobre todo cuando se asocia con dietas con bajo contenido de calcio. Contrariamente, los polifenoles han demostrado efectos beneficiosos a nivel del tejido oseo por su accion antioxidante. Se hallo asociacion entre la perdida osea con la edad y el estres oxidativo por la determinacion de productos avanzados de oxidacion de proteinas, malondialdehido y superoxido dismutasa en femures de ratas jovenes, adultas y de edad avanzada.Una publicacion previa mostro mayor DMO de columna lumbar (+9.7%) y cuello femoral (+6.2%) en mujeres pos...
Durante 20 años he trabajado sobre los efectos biológicos del flúor, tiempo en que he tropezado n... more Durante 20 años he trabajado sobre los efectos biológicos del flúor, tiempo en que he tropezado numerosas veces con grandes dificultades técnicas a la hora de medir la concentración de flúor en una muestra. Estas dificultades fueron sorteadas no sin esfuerzo y con la ayuda de mucha gente del Laboratorio de Biología Ósea. Hemos desarrollado varias técnicas para medir diferentes tipos de compuestos con flúor, las que posibilitaron importantes avances en el estudio de la biología del flúor y sus derivados. El trabajo constante en el tema me ha dado grandes satisfacciones y ha motivado la escritura de este libro que contiene qué se debe hacer en cada situación, detalles que habitualmente no se encuentran en la bibliografía consultada. Un objetivo menos visible es mi preocupación por la acumulación de flúor bajo diferentes formas químicas en el medio ambiente como consecuencia del uso indiscriminado de compuestos conteniendo este halógeno de propiedades fascinantes. Espero que este libro contribuya a que sean muchos los laboratorios que determinen flúor en el medio ambiente y sean muchas las voces que alerten sobre los efectos indeseables que comenzarán a ocurrir de alcanzarse valores críticos de fluoruro en el agua, suelo y aire de nuestro planeta. Agradezco la colaboración de los coautores de este libro y a quien me inició en el tema, el Dr. Rodolfo C. Puche, director del Laboratorio de Biología Ósea.
Abstract The osteoderms of Glyptodon reticulatus that do not belong to the cephalic shield, dorsa... more Abstract The osteoderms of Glyptodon reticulatus that do not belong to the cephalic shield, dorsal cuirass, or caudal tube are very variable morphologically. Their histological structure is also variable. Some lack a cancellous bone core, unlike those from the dorsal cuirass. One presents a few large cavities, whereas another is finely cancellous. Some present moderate remodeling and thick collagen fiber bundles. The moderate to high remodeling and the presence of fiber bundles perpendicular to the inner surface in some resemble many dorsal cuirass osteoderms of Glyptodon, but differ from previously described cuirass osteoderms of Glyptotherium. At least the perpendicular bundles may be useful to distinguish those glyptodontine genera. However, these characters do not allow distinction from Panochthus and Doedicurus. Histological distinction from sloth osteoderms is not possible because of the variability in the latter in remodeling degree, presence of large resorption spaces, and of an external fundamental system with fine fiber bundles perpendicular to the bone surface. An osteoderm presents evidence of circumferential lamellar accretion, as in dorsal cuirass osteoderms of Glyptodon. The lack of evidence of woven bone and of circumferential lamellar accretion, non-osteonal lamellar or parallel-fibered bone in another osteoderm suggests primary ossification was mostly metaplastic. This difference from the condition in Dasypus may depend of the time of appearance or body region.
Previous studies have demonstrated a negative correlation between intestinal alkaline phosphatase... more Previous studies have demonstrated a negative correlation between intestinal alkaline phosphatase (IAP) activity and calcium (Ca) absorption in the gut, as IAP acts as a protective mechanism inhibiting high Ca entry into enterocytes, preventing Ca overload. Here we evaluated Ca absorption and bone properties in knockout mice (KO) completely devoid of duodenal IAP (Akp3 −/− mice). Female C57BL/6 control mice (WT, n = 7) and KO mice (n = 10) were used to determine Ca absorption in vivo and by in situ isolated duodenal loops followed by histomorphometric analysis of duodenal villi and crypts. Bone mineral density, morphometry, histomorphometry and trabecular connectivity and biomechanical properties were measured on bones. We observed mild atrophy of the villi with lower absorption surface and a significantly higher Ca uptake in KO mice. While no changes were seen in cortical bone, we found better trabecular connectivity and biomechanical properties in the femurs of KO mice compared to WT mice. Our data indicate that IAP KO mice display higher intestinal Ca uptake, which over time appears to correlate with a positive effect on the biomechanical properties of trabecular bone.
Osteoporosis is a common bone disease characterized by low bone mass and altered bone microarchit... more Osteoporosis is a common bone disease characterized by low bone mass and altered bone microarchitecture, resulting in decreased bone strength with an increased risk of fractures. In clinical practice, physicians can assess the risk of fracture for a patient based on several risk factors. Some such as age, weight, and history of fractures after 50 years of age, parental fracture, smoking status, and alcohol intake are incorporated into FRAX, an assessment tool that estimates the 10-year probability of hip fracture and major osteoporotic fractures based on the individual's risk factors profile. The diagnosis of osteoporosis is currently based on bone mineral density (BMD) assessed by dual-energy X-ray absorptiometry scans. Among other widely recognized limitations of BMD is that BMD considers only the density of the bone and fails in measuring bone microarchitecture, for which novel techniques, such as trabecular bone score (TBS), have been developed. TBS is a texture parameter related to bone microarchitecture that may provide skeletal information that is not captured from the standard BMD measurement. Several studies have examined the value of TBS on predicting osteoporotic fractures. Our study aimed to summarize a review of the current scientific literature with focus on fracture risk assessment and to present both its findings and its conclusions regarding how and when TBS should be used. The existing literature indicates that low lumbar spine TBS is associated with a history of fracture and the incidence of new fracture. The effect is largely independent of BMD and of sufficient magnitude to enhance risk stratification with BMD. The TBS effect is also independent of FRAX, with likely greatest utility for those individuals whose BMD levels lie close to an intervention threshold. The clinical and scientific evidence supporting the use of TBS, with the ability of this technology to be seamlessly integrated into a daily workflow, makes TBS an attractive and useful clinical tool for physicians to improve patient management in osteoporosis. Further research is ongoing and necessary to further clarify the role of TBS in additional specific disorders.
Skeletal aging results in apoptosis of osteocytes, cells embedded in bone that control the genera... more Skeletal aging results in apoptosis of osteocytes, cells embedded in bone that control the generation/function of bone forming and resorbing cells. Aging also decreases connexin43 (Cx43) expression in bone; and osteocytic Cx43 deletion partially mimics the skeletal phenotype of old mice. Particularly, aging and Cx43 deletion increase osteocyte apoptosis, and osteoclast number and bone resorption on endocortical bone surfaces. We examined herein the molecular signaling events responsible for osteocyte apoptosis and osteoclast recruitment triggered by aging and Cx43 deficiency. Cx43-silenced MLO-Y4 osteocytic (Cx43 def) cells undergo spontaneous cell death in culture through caspase-3 activation and exhibit increased levels of apoptosis-related genes, and only transfection of Cx43 constructs able to form gap junction channels reverses Cx43 def cell death. Cx43 def cells and bones from old mice exhibit reduced levels of the prosurvival microRNA miR21 and, consistently, increased levels of the miR21 target phosphatase and tensin homolog (PTEN) and reduced phosphorylated Akt, whereas PTEN inhibition reduces Cx43 def cell apoptosis. miR21 reduction is sufficient to induce apoptosis of Cx43-expressing cells and miR21 deletion in miR21 fl/fl bones increases apoptosis-related gene expression, whereas a miR21 mimic prevents Cx43 def cell apoptosis, demonstrating that miR21 lies downstream of Cx43. Cx43 def cells release more osteoclastogenic cytokines [receptor activator of NFjB ligand (RANKL)/high-mobility group box-1 (HMGB1)], and caspase-3 inhibition prevents RANKL/HMGB1 release and the increased osteoclastogenesis induced by conditioned media from Cx43 def cells, which is blocked by antagonizing HMGB1-RAGE interaction. These findings identify a novel Cx43/miR21/HMGB1/RANKL pathway involved in preventing osteocyte apoptosis that also controls osteoclast formation/recruitment and is impaired with aging.
International journal of food sciences and nutrition, 2016
Dairy products are the main source of calcium (Ca), but the loss of the consumption habit contrib... more Dairy products are the main source of calcium (Ca), but the loss of the consumption habit contributes to low consumption in adulthood, which leads to osteoporosis and increased fracture risk. Domestic use of kefir is straightforward and the eggshell is a natural discarded source of Ca. This paper proposes the development of an enriched Ca reduced lactose milk using eggshell and kefir. During the in vitro preparation, the pH, Ca and lactose contents were measured. Ca intestinal absorption of untreated milk and milk with kefir was compared. Finally, human volunteers consumed this dairy product and 24-h urine Ca was measured. Results showed that the beverage has lower lactose and higher Ca than untreated milk and milk with kefir. Intestinal Ca absorption was not different between both milks and an increase in urinary Ca excretion was observed in humans. This study provides a methodology to prepare at home a dairy product that could contribute to improve the Ca intake in adults.
The aim of this work was to evaluate the effect of fluoride (F) on oxygen consumption (VO2) in ra... more The aim of this work was to evaluate the effect of fluoride (F) on oxygen consumption (VO2) in rats and how it might affect the respiratory chain and the levels of reactive oxygen species (ROS). Eighteen Sprague-Dawley rats were divided into three groups: Control, NaF20, and NaF40,which received 0, 20, and 40 µmol F/100 g bw/day for 30 days, respectively. In vivo,VO2 decreased 90 min after treatment with F, whereas TBARS, CAT, and GPx were higher. In vitro, F decreased VO2 in liver and in mitochondria. These results support the hypothesis that the bone inflammatory foci observed in treatments with NaF could involve an inhibition of the respiratory chain that would cause increase in reactive oxygen species (ROS).
Your article is protected by copyright and all rights are held exclusively by Springer Science +B... more Your article is protected by copyright and all rights are held exclusively by Springer Science +Business Media New York. This e-offprint is for personal use only and shall not be selfarchived in electronic repositories. If you wish to self-archive your article, please use the accepted manuscript version for posting on your own website. You may further deposit the accepted manuscript version in any repository, provided it is only made publicly available 12 months after official publication or later and provided acknowledgement is given to the original source of publication and a link is inserted to the published article on Springer's website. The link must be accompanied by the following text: "The final publication is available at link.springer.com".
Intestinal alkaline phosphatase (IAP) is a brush-border phosphomonoesterase. Its location suggest... more Intestinal alkaline phosphatase (IAP) is a brush-border phosphomonoesterase. Its location suggests an involvement in the uptake of nutrients, but its role has not yet been defined. IAP expression parallels that of other proteins involved in Ca absorption under vitamin D stimulation. Experiments carried outin vitrowith purified IAP have demonstrated an interaction between Ca and IAP. The gut is prepared to face different levels of Ca intake over time, but high Ca intake in a situation of a low-Ca diet over time would cause excessive entry of Ca into the enterocytes. The presence of a mechanism to block Ca entry and to avoid possible adverse effects is thus predictable. Thus, in the present study, Sprague–Dawley rats were fed with different amounts of Ca in the diet (0·2, 1 and 2 g%), and the percentage of Ca absorption (%Ca) in the presence and absence ofl-phenylalanine (Phe) was calculated. The presence of Phe caused a significant increase in %Ca (52·3 (sem6·5) % in the presence of ...
The osteocyte network is crucial for the response of bone to mechanical force. Within this networ... more The osteocyte network is crucial for the response of bone to mechanical force. Within this network, connexin43 (Cx43) is thought to mediate the communication of osteocytes and osteoblasts among themselves and the exchange of small molecules with the extracellular milieu. Despite recent advances in understanding Cx43 role for the response of bone cells to mechanical stimulation, the contribution of Cx43 specifically in osteocytes to mechanotransduction in vivo is not well-known. We examined the anabolic response to ulnar axial loading of mice lacking Cx43 in osteocytes (Cx43 Ot). Loading induced a greater increase in periosteal bone formation rate in Cx43 Ot mice compared to control littermates, resulting from higher mineralizing surface and enhanced mineral apposition rate. Expression of-catenin protein, a molecule implicated in mechanotransduction, was higher in bones from Cx43 Ot mice, compared to littermate controls. In addition, MLO-Y4 osteocytic cells knocked-down for Cx43 exhibited higher-catenin protein expression and enhanced response to mechanical stimulation. These findings suggest that osteocytes lacking Cx43 are "primed" to respond to mechanical stimulation and that absence of Cx43 in osteocytes unleashes bone formation, by a mechanism that might involve accumulation of-catenin.
Connexin 43 (Cx43) mediates osteocyte communication with other cells and with the extracellular m... more Connexin 43 (Cx43) mediates osteocyte communication with other cells and with the extracellular milieu and regulates osteoblastic cell signaling and gene expression. We now report that mice lacking Cx43 in osteoblasts/osteocytes or only in osteocytes (Cx43 ΔOt mice) exhibit increased osteocyte apoptosis, endocortical resorption and periosteal bone formation, resulting in higher marrow cavity and total tissue areas measured at the femoral mid-diaphysis. Blockade of resorption reversed the increased marrow cavity but not total tissue area, demonstrating that endocortical resorption and periosteal apposition are independently regulated. Anatomical mapping of apoptotic osteocytes, osteocytic protein expression, and resorption and formation, suggests that Cx43 controls osteoclast and osteoblast activity by regulating osteoprotegerin and sclerostin levels, respectively, in osteocytes located in specific areas of the cortex. Whereas empty lacunae and living osteocytes lacking osteoprotegerin were distributed throughout cortical bone in Cx43 ΔOt mice, apoptotic osteocytes were preferentially located in areas containing osteoclasts, suggesting that osteoclast recruitment requires active signaling from dying osteocytes. Furthermore, Cx43 deletion in cultured osteocytic cells resulted in increased apoptosis and decreased osteoprotegerin expression. Thus, Cx43 is essential in a cell-autonomous fashion in vivo and in vitro for osteocyte survival and for controlling the expression of osteocytic genes that affect osteoclast and osteoblast function.
This paper describes a novel methodology for the simultaneous estimation of bone formation (BF) a... more This paper describes a novel methodology for the simultaneous estimation of bone formation (BF) and resorption (BR) in rats using fluoride as a nonradioactive bone-seeker ion. The pharmacokinetics of flouride have been extensively studied in rats; its constants have all been characterized. This knowledge was the cornerstone for the underlying mathematical model that we used to measure bone fluoride uptake and elimination rate after a dose of fluoride. Bone resorption and formation were estimated by bone fluoride uptake and elimination rate, respectively. ROC analysis showed that sensitivity, specificity and area under the ROC curve were not different from deoxypiridinoline and bone alkaline phosphatase, well-known bone markers. Sprague-Dawley rats with modified bone remodelling (ovariectomy, hyper, and hypocalcic diet, antiresorptive treatment) were used to validate the values obtained with this methodology. The results of BF and BR obtained with this technique were as expected for each biological model. Although the method should be performed under general anesthesia, it has several advantages: simultaneous measurement of BR and BF, low cost, and the use of compounds with no expiration date.
were closer than those found for the cortical vBMD in fertile individuals. All relationships were... more were closer than those found for the cortical vBMD in fertile individuals. All relationships were independent of age before menopause, TMP being an additional determinant for both radius and tibia features. Concerning the mechanical influences on the skeleton, the selected mechanical factors (regional muscle size, bone lever lengths) would be more relevant than the selected, age-related or anthropometric determinants or confounders to the determination of the allometrically-associated bone properties (mass, design, strength), yet not to that of bone "intensive" properties as cortical vBMD. Concerning the endocrine-metabolic influences, the mechanical impacts of muscles and bone levers on bone structure were comparable in men and pre-MP women, but TMP could exert a stronger impact than other, allometric or mechanical determinants did on any kind of bone property, including the vCtD, and probably excepting the diaphyseal design.
Purpose. To evaluate the effect of teriparatide (TPTD) on bone mineral density (BMD) and bone mar... more Purpose. To evaluate the effect of teriparatide (TPTD) on bone mineral density (BMD) and bone markers under clinical practice conditions. To assess whether the results in real-life match those published in clinical trials. Methods. Cross-sectional study of postmenopausal women treated with TPTD for at least 12 months. Results. 264 patients were included in the study. Main characteristics are as follows: age: 68.7 ± 10.2 years, previous fractures: 57.6%, and previously treated with antiresorptive (AR-prior): 79%. All bone turnover markers studied significantly increased after 6 months. CTX and BGP remained high up to 24 months, but total and bone alkaline phosphatase returned to basal values at month 18. There was a significant increase in lumbar spine (LS) BMD after 6 months (+6.2%), with a maximum peak at 24 months (+13%). Femoral neck (FN) and total hip (TH) BMD showed a significant increase later than LS (just at month 12), reaching a maximum peak at month 24 (FN + 7.9% and TH + ...
Heterotopic ossification (HO) is the formation of extraskeletal bone in muscle and soft tissues a... more Heterotopic ossification (HO) is the formation of extraskeletal bone in muscle and soft tissues and could be genetic or non-genetic. The classic presentation of non-genetic HO is in young adults with a clear history of local trauma, surgery or prolonged immobilization after spinal cord and traumatic brain injuries. Genetic HO has a significant clinical severity compared to non-genetic causes and includes fibrodysplasia ossificans progressiva (FOP). FOP is an extremely rare genetic skeletal disorder characterized by congenital malformations of the great toes and progressive heterotopic ossification that forms qualitatively normal bone in characteristic extraskeletal sites affecting skeletal muscles, fascia, tendons, and ligaments. Previously, it has been reported an association between SARS-CoV-2 infection (COVID-19) and HO or FOP exacerbation with unclear etiopathogenesis. The possible mechanisms could be prolonged immobilization and systemic inflammation. Here, we describe the case of a 55-year-old apparently healthy man who suffered from a severe SARS-CoV-2 infection after that he experienced an extensive and progressive heterotopic ossification around the shoulders, the elbows, the hip, the knees, and the ankles. Because of the clinical severity, the painful soft-tissue swelling, the progressive HO, and the bilateral congenital hallux valgus deformity, a late-onset atypical FOP was suspected. Nevertheless, no variant of clinical significance has been identified in the coding regions and splicing sites in the ACVR1 gene and no deletions and/or duplications have been identified in exonic regions.
Existe la creencia popular que el consumo habitual de yerba mate (YM) provoca acidez o gastritis.... more Existe la creencia popular que el consumo habitual de yerba mate (YM) provoca acidez o gastritis. De hecho, en internet aparece gran cantidad de informacion sobre ello y multiples recomendaciones medicas. Sin embargo, la evidencia cientifica al respecto es pobre.
El consumo de yerba mate (Ilex paraguariensis) es muy frecuente en varios paises de America Latin... more El consumo de yerba mate (Ilex paraguariensis) es muy frecuente en varios paises de America Latina. Varios fitoquimicos activos como xantinas (cafeina) y polifenoles (acido clorogenico, quercetina, rutina) han sido identificados en extractos acuosos de Ilex paraguariensis. Entre los componentes de la yerba mate con efecto sobre el tejido oseo se destaca que la cafeina en altas concentraciones tendria un impacto negativo sobre la densidad mineral osea (DMO) sobre todo cuando se asocia con dietas con bajo contenido de calcio. Contrariamente, los polifenoles han demostrado efectos beneficiosos a nivel del tejido oseo por su accion antioxidante. Se hallo asociacion entre la perdida osea con la edad y el estres oxidativo por la determinacion de productos avanzados de oxidacion de proteinas, malondialdehido y superoxido dismutasa en femures de ratas jovenes, adultas y de edad avanzada.Una publicacion previa mostro mayor DMO de columna lumbar (+9.7%) y cuello femoral (+6.2%) en mujeres pos...
Durante 20 años he trabajado sobre los efectos biológicos del flúor, tiempo en que he tropezado n... more Durante 20 años he trabajado sobre los efectos biológicos del flúor, tiempo en que he tropezado numerosas veces con grandes dificultades técnicas a la hora de medir la concentración de flúor en una muestra. Estas dificultades fueron sorteadas no sin esfuerzo y con la ayuda de mucha gente del Laboratorio de Biología Ósea. Hemos desarrollado varias técnicas para medir diferentes tipos de compuestos con flúor, las que posibilitaron importantes avances en el estudio de la biología del flúor y sus derivados. El trabajo constante en el tema me ha dado grandes satisfacciones y ha motivado la escritura de este libro que contiene qué se debe hacer en cada situación, detalles que habitualmente no se encuentran en la bibliografía consultada. Un objetivo menos visible es mi preocupación por la acumulación de flúor bajo diferentes formas químicas en el medio ambiente como consecuencia del uso indiscriminado de compuestos conteniendo este halógeno de propiedades fascinantes. Espero que este libro contribuya a que sean muchos los laboratorios que determinen flúor en el medio ambiente y sean muchas las voces que alerten sobre los efectos indeseables que comenzarán a ocurrir de alcanzarse valores críticos de fluoruro en el agua, suelo y aire de nuestro planeta. Agradezco la colaboración de los coautores de este libro y a quien me inició en el tema, el Dr. Rodolfo C. Puche, director del Laboratorio de Biología Ósea.
Abstract The osteoderms of Glyptodon reticulatus that do not belong to the cephalic shield, dorsa... more Abstract The osteoderms of Glyptodon reticulatus that do not belong to the cephalic shield, dorsal cuirass, or caudal tube are very variable morphologically. Their histological structure is also variable. Some lack a cancellous bone core, unlike those from the dorsal cuirass. One presents a few large cavities, whereas another is finely cancellous. Some present moderate remodeling and thick collagen fiber bundles. The moderate to high remodeling and the presence of fiber bundles perpendicular to the inner surface in some resemble many dorsal cuirass osteoderms of Glyptodon, but differ from previously described cuirass osteoderms of Glyptotherium. At least the perpendicular bundles may be useful to distinguish those glyptodontine genera. However, these characters do not allow distinction from Panochthus and Doedicurus. Histological distinction from sloth osteoderms is not possible because of the variability in the latter in remodeling degree, presence of large resorption spaces, and of an external fundamental system with fine fiber bundles perpendicular to the bone surface. An osteoderm presents evidence of circumferential lamellar accretion, as in dorsal cuirass osteoderms of Glyptodon. The lack of evidence of woven bone and of circumferential lamellar accretion, non-osteonal lamellar or parallel-fibered bone in another osteoderm suggests primary ossification was mostly metaplastic. This difference from the condition in Dasypus may depend of the time of appearance or body region.
Previous studies have demonstrated a negative correlation between intestinal alkaline phosphatase... more Previous studies have demonstrated a negative correlation between intestinal alkaline phosphatase (IAP) activity and calcium (Ca) absorption in the gut, as IAP acts as a protective mechanism inhibiting high Ca entry into enterocytes, preventing Ca overload. Here we evaluated Ca absorption and bone properties in knockout mice (KO) completely devoid of duodenal IAP (Akp3 −/− mice). Female C57BL/6 control mice (WT, n = 7) and KO mice (n = 10) were used to determine Ca absorption in vivo and by in situ isolated duodenal loops followed by histomorphometric analysis of duodenal villi and crypts. Bone mineral density, morphometry, histomorphometry and trabecular connectivity and biomechanical properties were measured on bones. We observed mild atrophy of the villi with lower absorption surface and a significantly higher Ca uptake in KO mice. While no changes were seen in cortical bone, we found better trabecular connectivity and biomechanical properties in the femurs of KO mice compared to WT mice. Our data indicate that IAP KO mice display higher intestinal Ca uptake, which over time appears to correlate with a positive effect on the biomechanical properties of trabecular bone.
Osteoporosis is a common bone disease characterized by low bone mass and altered bone microarchit... more Osteoporosis is a common bone disease characterized by low bone mass and altered bone microarchitecture, resulting in decreased bone strength with an increased risk of fractures. In clinical practice, physicians can assess the risk of fracture for a patient based on several risk factors. Some such as age, weight, and history of fractures after 50 years of age, parental fracture, smoking status, and alcohol intake are incorporated into FRAX, an assessment tool that estimates the 10-year probability of hip fracture and major osteoporotic fractures based on the individual's risk factors profile. The diagnosis of osteoporosis is currently based on bone mineral density (BMD) assessed by dual-energy X-ray absorptiometry scans. Among other widely recognized limitations of BMD is that BMD considers only the density of the bone and fails in measuring bone microarchitecture, for which novel techniques, such as trabecular bone score (TBS), have been developed. TBS is a texture parameter related to bone microarchitecture that may provide skeletal information that is not captured from the standard BMD measurement. Several studies have examined the value of TBS on predicting osteoporotic fractures. Our study aimed to summarize a review of the current scientific literature with focus on fracture risk assessment and to present both its findings and its conclusions regarding how and when TBS should be used. The existing literature indicates that low lumbar spine TBS is associated with a history of fracture and the incidence of new fracture. The effect is largely independent of BMD and of sufficient magnitude to enhance risk stratification with BMD. The TBS effect is also independent of FRAX, with likely greatest utility for those individuals whose BMD levels lie close to an intervention threshold. The clinical and scientific evidence supporting the use of TBS, with the ability of this technology to be seamlessly integrated into a daily workflow, makes TBS an attractive and useful clinical tool for physicians to improve patient management in osteoporosis. Further research is ongoing and necessary to further clarify the role of TBS in additional specific disorders.
Skeletal aging results in apoptosis of osteocytes, cells embedded in bone that control the genera... more Skeletal aging results in apoptosis of osteocytes, cells embedded in bone that control the generation/function of bone forming and resorbing cells. Aging also decreases connexin43 (Cx43) expression in bone; and osteocytic Cx43 deletion partially mimics the skeletal phenotype of old mice. Particularly, aging and Cx43 deletion increase osteocyte apoptosis, and osteoclast number and bone resorption on endocortical bone surfaces. We examined herein the molecular signaling events responsible for osteocyte apoptosis and osteoclast recruitment triggered by aging and Cx43 deficiency. Cx43-silenced MLO-Y4 osteocytic (Cx43 def) cells undergo spontaneous cell death in culture through caspase-3 activation and exhibit increased levels of apoptosis-related genes, and only transfection of Cx43 constructs able to form gap junction channels reverses Cx43 def cell death. Cx43 def cells and bones from old mice exhibit reduced levels of the prosurvival microRNA miR21 and, consistently, increased levels of the miR21 target phosphatase and tensin homolog (PTEN) and reduced phosphorylated Akt, whereas PTEN inhibition reduces Cx43 def cell apoptosis. miR21 reduction is sufficient to induce apoptosis of Cx43-expressing cells and miR21 deletion in miR21 fl/fl bones increases apoptosis-related gene expression, whereas a miR21 mimic prevents Cx43 def cell apoptosis, demonstrating that miR21 lies downstream of Cx43. Cx43 def cells release more osteoclastogenic cytokines [receptor activator of NFjB ligand (RANKL)/high-mobility group box-1 (HMGB1)], and caspase-3 inhibition prevents RANKL/HMGB1 release and the increased osteoclastogenesis induced by conditioned media from Cx43 def cells, which is blocked by antagonizing HMGB1-RAGE interaction. These findings identify a novel Cx43/miR21/HMGB1/RANKL pathway involved in preventing osteocyte apoptosis that also controls osteoclast formation/recruitment and is impaired with aging.
International journal of food sciences and nutrition, 2016
Dairy products are the main source of calcium (Ca), but the loss of the consumption habit contrib... more Dairy products are the main source of calcium (Ca), but the loss of the consumption habit contributes to low consumption in adulthood, which leads to osteoporosis and increased fracture risk. Domestic use of kefir is straightforward and the eggshell is a natural discarded source of Ca. This paper proposes the development of an enriched Ca reduced lactose milk using eggshell and kefir. During the in vitro preparation, the pH, Ca and lactose contents were measured. Ca intestinal absorption of untreated milk and milk with kefir was compared. Finally, human volunteers consumed this dairy product and 24-h urine Ca was measured. Results showed that the beverage has lower lactose and higher Ca than untreated milk and milk with kefir. Intestinal Ca absorption was not different between both milks and an increase in urinary Ca excretion was observed in humans. This study provides a methodology to prepare at home a dairy product that could contribute to improve the Ca intake in adults.
The aim of this work was to evaluate the effect of fluoride (F) on oxygen consumption (VO2) in ra... more The aim of this work was to evaluate the effect of fluoride (F) on oxygen consumption (VO2) in rats and how it might affect the respiratory chain and the levels of reactive oxygen species (ROS). Eighteen Sprague-Dawley rats were divided into three groups: Control, NaF20, and NaF40,which received 0, 20, and 40 µmol F/100 g bw/day for 30 days, respectively. In vivo,VO2 decreased 90 min after treatment with F, whereas TBARS, CAT, and GPx were higher. In vitro, F decreased VO2 in liver and in mitochondria. These results support the hypothesis that the bone inflammatory foci observed in treatments with NaF could involve an inhibition of the respiratory chain that would cause increase in reactive oxygen species (ROS).
Your article is protected by copyright and all rights are held exclusively by Springer Science +B... more Your article is protected by copyright and all rights are held exclusively by Springer Science +Business Media New York. This e-offprint is for personal use only and shall not be selfarchived in electronic repositories. If you wish to self-archive your article, please use the accepted manuscript version for posting on your own website. You may further deposit the accepted manuscript version in any repository, provided it is only made publicly available 12 months after official publication or later and provided acknowledgement is given to the original source of publication and a link is inserted to the published article on Springer's website. The link must be accompanied by the following text: "The final publication is available at link.springer.com".
Intestinal alkaline phosphatase (IAP) is a brush-border phosphomonoesterase. Its location suggest... more Intestinal alkaline phosphatase (IAP) is a brush-border phosphomonoesterase. Its location suggests an involvement in the uptake of nutrients, but its role has not yet been defined. IAP expression parallels that of other proteins involved in Ca absorption under vitamin D stimulation. Experiments carried outin vitrowith purified IAP have demonstrated an interaction between Ca and IAP. The gut is prepared to face different levels of Ca intake over time, but high Ca intake in a situation of a low-Ca diet over time would cause excessive entry of Ca into the enterocytes. The presence of a mechanism to block Ca entry and to avoid possible adverse effects is thus predictable. Thus, in the present study, Sprague–Dawley rats were fed with different amounts of Ca in the diet (0·2, 1 and 2 g%), and the percentage of Ca absorption (%Ca) in the presence and absence ofl-phenylalanine (Phe) was calculated. The presence of Phe caused a significant increase in %Ca (52·3 (sem6·5) % in the presence of ...
The osteocyte network is crucial for the response of bone to mechanical force. Within this networ... more The osteocyte network is crucial for the response of bone to mechanical force. Within this network, connexin43 (Cx43) is thought to mediate the communication of osteocytes and osteoblasts among themselves and the exchange of small molecules with the extracellular milieu. Despite recent advances in understanding Cx43 role for the response of bone cells to mechanical stimulation, the contribution of Cx43 specifically in osteocytes to mechanotransduction in vivo is not well-known. We examined the anabolic response to ulnar axial loading of mice lacking Cx43 in osteocytes (Cx43 Ot). Loading induced a greater increase in periosteal bone formation rate in Cx43 Ot mice compared to control littermates, resulting from higher mineralizing surface and enhanced mineral apposition rate. Expression of-catenin protein, a molecule implicated in mechanotransduction, was higher in bones from Cx43 Ot mice, compared to littermate controls. In addition, MLO-Y4 osteocytic cells knocked-down for Cx43 exhibited higher-catenin protein expression and enhanced response to mechanical stimulation. These findings suggest that osteocytes lacking Cx43 are "primed" to respond to mechanical stimulation and that absence of Cx43 in osteocytes unleashes bone formation, by a mechanism that might involve accumulation of-catenin.
Connexin 43 (Cx43) mediates osteocyte communication with other cells and with the extracellular m... more Connexin 43 (Cx43) mediates osteocyte communication with other cells and with the extracellular milieu and regulates osteoblastic cell signaling and gene expression. We now report that mice lacking Cx43 in osteoblasts/osteocytes or only in osteocytes (Cx43 ΔOt mice) exhibit increased osteocyte apoptosis, endocortical resorption and periosteal bone formation, resulting in higher marrow cavity and total tissue areas measured at the femoral mid-diaphysis. Blockade of resorption reversed the increased marrow cavity but not total tissue area, demonstrating that endocortical resorption and periosteal apposition are independently regulated. Anatomical mapping of apoptotic osteocytes, osteocytic protein expression, and resorption and formation, suggests that Cx43 controls osteoclast and osteoblast activity by regulating osteoprotegerin and sclerostin levels, respectively, in osteocytes located in specific areas of the cortex. Whereas empty lacunae and living osteocytes lacking osteoprotegerin were distributed throughout cortical bone in Cx43 ΔOt mice, apoptotic osteocytes were preferentially located in areas containing osteoclasts, suggesting that osteoclast recruitment requires active signaling from dying osteocytes. Furthermore, Cx43 deletion in cultured osteocytic cells resulted in increased apoptosis and decreased osteoprotegerin expression. Thus, Cx43 is essential in a cell-autonomous fashion in vivo and in vitro for osteocyte survival and for controlling the expression of osteocytic genes that affect osteoclast and osteoblast function.
This paper describes a novel methodology for the simultaneous estimation of bone formation (BF) a... more This paper describes a novel methodology for the simultaneous estimation of bone formation (BF) and resorption (BR) in rats using fluoride as a nonradioactive bone-seeker ion. The pharmacokinetics of flouride have been extensively studied in rats; its constants have all been characterized. This knowledge was the cornerstone for the underlying mathematical model that we used to measure bone fluoride uptake and elimination rate after a dose of fluoride. Bone resorption and formation were estimated by bone fluoride uptake and elimination rate, respectively. ROC analysis showed that sensitivity, specificity and area under the ROC curve were not different from deoxypiridinoline and bone alkaline phosphatase, well-known bone markers. Sprague-Dawley rats with modified bone remodelling (ovariectomy, hyper, and hypocalcic diet, antiresorptive treatment) were used to validate the values obtained with this methodology. The results of BF and BR obtained with this technique were as expected for each biological model. Although the method should be performed under general anesthesia, it has several advantages: simultaneous measurement of BR and BF, low cost, and the use of compounds with no expiration date.
were closer than those found for the cortical vBMD in fertile individuals. All relationships were... more were closer than those found for the cortical vBMD in fertile individuals. All relationships were independent of age before menopause, TMP being an additional determinant for both radius and tibia features. Concerning the mechanical influences on the skeleton, the selected mechanical factors (regional muscle size, bone lever lengths) would be more relevant than the selected, age-related or anthropometric determinants or confounders to the determination of the allometrically-associated bone properties (mass, design, strength), yet not to that of bone "intensive" properties as cortical vBMD. Concerning the endocrine-metabolic influences, the mechanical impacts of muscles and bone levers on bone structure were comparable in men and pre-MP women, but TMP could exert a stronger impact than other, allometric or mechanical determinants did on any kind of bone property, including the vCtD, and probably excepting the diaphyseal design.
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