Bone and bone marrow pro-osteoclastogenic cytokines are up-regulated in osteoporosis fragility fractures

Summary

This study evaluates cytokines production in bone and bone marrow of patients with an osteoporotic fracture or with osteoarthritis by real time PCR, Western blot and immunohistochemistry. We demonstrate that the cytokine pattern is shifted towards osteoclast activation and osteoblast inhibition in patients with osteoporotic fractures.

Introduction

Fragility fractures are the resultant of low bone mass and poor bone architecture typical of osteoporosis. Cytokines involved in the control of bone cell maturation and function are produced by both bone itself and bone marrow cells, but the roles of these two sources in its control and the amounts they produce are not clear. This study compares their production in patients with an osteoporotic fracture and those with osteoarthritis.

Methods

We evaluated 52 femoral heads from women subjected to hip-joint replacement surgery for femoral neck fractures due to low-energy trauma (37), or for osteoarthritis (15). Total RNA was extracted from both bone and bone marrow, and quantitative PCR was used to identify the receptor activator of nuclear factor kB Ligand (RANKL), osteoprotegerin (OPG), macrophage colony stimulating factor (M-CSF), transforming growth factor ?? (TGF??), Dickoppf-1 (DKK-1) and sclerostin (SOST) expression. Immunohistochemistry and Western blot were performed in order to quantify and localize in bone and bone marrow the cytokines.

Results

We found an increase of RANKL/OPG ratio, M-CSF, SOST and DKK-1 in fractured patients, whereas TGF?? was increased in osteoarthritic bone. Bone marrow produced greater amounts of RANKL, M-CSF and TGF?? compared to bone, whereas the production of DKK-1 and SOST was higher in bone.

Conclusions

We show that bone marrow cells produced the greater amount of pro-osteoclastogenic cytokines, whereas bone cells produced higher amount of osteoblast inhibitors in patients with fragility fracture, thus the cytokine pattern is shifted towards osteoclast activation and osteoblast inhibition in these patients.     

Polycythemia is associated with bone loss and reduced osteoblast activity in mice

Summary

Increased fragility has been described in humans with polycythemia vera (PV). Herein, we describe an osteoporotic phenotype associated with decreased osteoblast activity in a mouse model of PV and another mouse of polycythemia and elevated circulating erythropoietin (EPO). Our results are important for patients with PV or those treated with recombinant EPO (rEPO).

Introduction

PV and other myeloproliferative syndromes have been recently associated with an increased risk for fractures. However, the presence of osteoporosis in these patients has not been well documented. EPO, a hormone primarily known to stimulate erythropoiesis, has been shown recently to regulate bone homeostasis in mice. The aim of this study was to examine the bone phenotype of a mouse model of PV and compare it to that of animals with polycythemia caused by elevated circulating EPO.

Methods

Bone mass and remodeling were evaluated by micro-computed tomography and histomorphometry. The JAK2^V617F knock-in mouse, a model of human PV, manifests polycythemia and low circulating EPO levels. Results from this mouse were compared to wild type (wt) controls and the tg6 transgenic mouse that shows polycythemia caused by increased constitutive expression of EPO.

Results

Compared to wt, both JAK2^V617F and tg6 mice had a decrease in trabecular bone mass. Tg6 mice showed an additional modest decrease in cortical thickness and cortical bone volume per tissue volume (P?<?0.01) suggesting a more severe bone phenotype than JAK2^V617F. Decreased osteoblast numbers and bone formation along with normal osteoclast numbers and activity were found in both mice.

Conclusions

This study indicates that PV is associated with low bone mass and decreased osteoblast activity in mice. Our results support future studies of osteoporosis in affected humans. Polycythemia caused by chronically elevated circulating EPO also results in bone loss, and implications on patients treated with rEPO should be evaluated.

     

An experimental therapy to improve skeletal growth and prevent bone loss in a mouse model overexpressing IL-6

Summary

Premature osteoporosis and stunted growth are common complications of childhood chronic inflammatory disease. Presently, no treatment regimens are available for these defects in juvenile diseases. We identified the sequential Fc-OPG/hPTH treatment as an experimental therapy that improves the skeletal growth and prevents the bone loss in a mouse model overexpressing IL-6.

Introduction

Premature osteoporosis and stunted growth are common complications of childhood chronic inflammatory diseases and have a significant impact on patients’ quality of life. Presently, no treatment regimens are available for these defects in juvenile diseases. To test a new therapeutic approach, we used growing mice overexpressing the pro-inflammatory cytokine IL-6 (TG), which show a generalized bone loss and stunted growth.

Methods

Since TG mice present increased bone resorption and impaired bone formation, we tested a combined therapy with the antiresorptive modified osteoprotegerin, Fc-OPG, and the anabolic PTH. We injected TG mice with Fc-OPG once at the 4th day of life and with hPTH(1–34) everyday from the 16th to the 30th day of age.

Results

A complete prevention of growth and bone defects was observed in treated mice due to normalization of osteoclast and osteoblast parameters. Re-establishment of normal bone turnover was confirmed by RT-PCR analysis and by in vitro experiments that revealed the full rescue of osteoclast and osteoblast functions. The phenotypic recovery of TG mice was due to the sequential treatment, because TG mice treated with Fc-OPG or hPTH alone showed an increase of body weight, tibia length, and bone volume to intermediate levels between those observed in vehicle-treated WT and TG mice.

Conclusions

Our results identified the sequential Fc-OPG/hPTH treatment as an experimental therapy that improves the skeletal growth and prevents the bone loss in IL-6 overexpressing mice, thus providing the proof of principle for a therapeutic approach to correct these defects in juvenile inflammatory diseases.     

Teriparatide increases the maturation of circulating osteoblast precursors

Summary

This study shows that teriparatide promotes the circulating osteoblast (OB) precursor degree of maturation in patients affected by postmenopausal osteoporosis.

Introduction

Anabolic treatment with teriparatide has proven effective for the therapy of postmenopausal osteoporosis and significantly reduces the risk of non-vertebral fragility fractures. The aim of this study was to investigate the effect of teriparatide on circulating OB precursors.

Methods

We evaluated by flow cytometry and real-time PCR the expression of OBs typical markers in peripheral blood mononuclear cells during treatment with teriparatide plus calcium and vitamin D, raloxifene plus calcium and vitamin D or calcium and vitamin D alone at various time points. Serum bone alkaline phosphatase and osteocalcin (OC) were measured as markers of bone turnover.

Results

Our results show that circulating OB precursors are more numerous and more immature in patients affected by fragility fractures than in osteoporotic patients without fractures. We also show that teriparatide treatment increases the expression of alkaline phosphatase and of OC in OB precursors; thus, it increases their degree of maturation.

Conclusions

We suggest that teriparatide acts as anabolic agents also by promoting the maturation of OB precursors.     

Calcium Phosphate Cement with BMP-2-loaded Gelatin Microspheres Enhances Bone Healing in Osteoporosis: A Pilot Study

Background

The capacity for bone healing reportedly is limited in osteoporosis with a less than ideal environment for healing of bone grafts. We therefore developed a composite bone substitute with rhBMP-2 loaded gelatin microsphere (GM) and calcium phosphate cement (CPC) to use in osteoporosis.

Questions/purposes

We asked whether (1) controlled release of rhBMP-2 could be improved in this composite bone substitute and (2) increasing factors released from the bone substitute could accelerate osteoporotic bone healing.

Methods

We soaked rhBMP-2/GM/CPC and rhBMP-2/CPC composites in simulated body fluid for 28 days and then determined the amount of rhBMP-2 released. Both composites were implanted in bone defects of osteoporotic goats and left in place for 45 and 140 days; the specimens then were evaluated mechanically (pushout test) and morphologically (CT scanning, histology).

Results

The in vitro study showed the new composite released more rhBMP-2 compared with rhBMP-2/CPC. CT showed the defects healed more quickly with new grafts. The bone mineralization rate was greater in rhBMP-2/GM/CPC than in rhBMP-2/CPC after 45 days of implantation and the pushout test was stronger after 45 and 140 days of implantation.

Conclusions

The new graft composite released more loaded factors and appeared to repair osteoporotic bone defects.

Clinical Relevance

These preliminary data suggest the new composite can be used as a bone substitute to accelerate healing of fractures and bone defects in osteoporosis.     

Spinal cord injury causes rapid osteoclastic resorption and growth plate abnormalities in growing rats (SCI-induced bone loss in growing rats)

Summary

Spinal cord injury causes severe bone loss. We report osteoclast resorption with severe trabecular and cortical bone loss, decreased bone mineral apposition, and growth plate abnormalities in a rodent model of contusion spinal cord injury. These findings will help elucidate the mechanisms of osteoporosis following neurological trauma.

Introduction

Limited understanding of the mechanism(s) that underlie spinal cord injury (SCI)-induced bone loss has led to few treatment options. As SCI-induced osteoporosis carries significant morbidity and can worsen already profound disability, there is an urgency to advance knowledge regarding this pathophysiology.

Methods

A clinically relevant contusion model of experimental spinal cord injury was used to generate severe lower thoracic SCI by weight-drop (10 g?×?50 mm) in adolescent male Sprague-Dawley rats. Body weight and gender-matched naïve (no surgery) rats served as controls. Bone microarchitecture was determined by micro-computed tomographic imaging. Mature osteoclasts were identified by TRAP staining and bone apposition rate was determined by dynamic histomorphometry.

Results

At 10 days post-injury we detected a marked 48% decrease in trabecular bone and a 35% decrease in cortical bone at the distal femoral metaphysis by micro-CT. A 330% increase in the number of mature osteoclasts was detected at the growth plate in the injured animals that corresponded with cellular disorganization at the chondro-osseous junction. Appositional growth studies demonstrated decreased new bone formation with a mineralization defect indicative of osteoblast dysfunction.

Conclusions

Contusion SCI results in a rapid bone loss that is the result of increased bone resorption and decreased bone formation.     

Social inequalities in osteoporosis and fracture among community-dwelling older men and women: findings from the Hertfordshire cohort study

Summary

It is unknown whether osteoporosis is socially patterned. Using data from the Hertfordshire Cohort Study we found no consistent evidence for social inequalities in prevalent or incident fracture, bone mineral density or loss rates, or bone strength. Public health strategies for prevention of osteoporosis should focus on the whole population.

Introduction

Osteoporosis and osteoporotic fracture are major public health issues for society; the burden for the affected individual is also high. It is unclear whether osteoporosis and osteoporotic fracture are socially patterned.

Objective

This study aims to analyse social inequalities in osteoporosis and osteoporotic fracture among the 3,225 community-dwelling men and women, aged 59?C73?years, who participated in the Hertfordshire Cohort Study (HCS), UK.

Methods

A panel of markers of bone health (fracture since 45?years of age; DXA bone mineral density and loss rate at the total femur; pQCT strength strain indices for the radius and tibia; and incident fracture) were analysed in relation to the social circumstances of the HCS participants (characterised at the individual level by: age left full time education; current social class; housing tenure and car availability).

Results

We found little strong or consistent evidence among men, or women, for social inequalities in prevalent or incident fracture, DXA bone mineral density, bone loss rates, or pQCT bone strength, with or without adjustment for age, anthropometry, lifestyle and clinical characteristics. Reduced car availability at baseline was associated with lower pQCT radius and tibia strength strain indices at follow-up among men only (p?=?0.02 radius and p?<?0.01 tibia unadjusted; p?=?0.05 radius and p?=?0.01 tibia, adjusted for age, anthropometry, lifestyle and clinical characteristics).

Conclusions

Our results suggest that fracture and osteoporosis do not have a strong direct social gradient and that public health strategies for prevention and treatment of osteoporosis should continue to focus on the whole population.     

Short-term glucocorticoid treatment causes spinal osteoporosis in ovariectomized rats

Purpose

In humans, glucocorticoid-induced osteoporosis is the most common cause of medication-induced osteoporosis. Recent clinical data suggest that glucocorticoid therapy increases the risk of vertebral fractures within a short treatment period. Therefore, this study aimed at investigating vertebral bone in a rat model of glucocorticoid-induced postmenopausal osteoporosis.

Methods

Fifty Sprague–Dawley rats were randomly assigned into three groups: 1) untreated controls, 2) Sham-operated group, and 3) ovariectomized rats treated with glucocorticoid (dexamethasone) for 3 months (3M) after recovery from bilateral ovariectomy. Osteoporotic bone status was determined by means of the gold standard dual energy X-ray absorptiometry (DEXA) scan. Vertebral bodies were examined using µCT, histological analysis, mRNA expression analysis, and biomechanical compression testing. Further systemic effects were studied biochemically using serum marker analysis.

Results

Dexamethasone treatment showed at 3M a significantly lower bone mineral density in ovariectomized rats compared to Sham-operated control (p < 0.0001) as analyzed in vivo by DEXA. Furthermore, Z scores reached levels of ?5.7 in the spine indicating sever osteoporotic bone status. Biomechanical testing of compression stability indicated a lower functional competence (p < 0.0001) in the spine of treated rats. µCT analysis showed significant reduction of bone volume density (BV/TV%; p < 0.0001), significantly enhanced trabecular spacing (Tb.Sp; p < 0.0001) with less trabecular number (Tb.N; p < 0.001) and complete loss of trabecular structures in glucocorticoid-treated ovariectomized rats. Histological analysis by osteoblast and osteoclast activities reflected a higher bone catabolism reflected by osteoclast counts by TRAP (p < 0.019) and lower bone catabolism indicated by ALP-stained area (p < 0.035).Serum analysis showed a significant increase in osteocalcin (p < 0.0001), osteopontin (p < 0.01) and insulin (p < 0.001) at 3M. Expression analysis of molecular markers in the vertebral body revealed lower expression in tenascin C in the OVX-steroid animals at 3M.

Conclusions

Short-term glucocorticoid treatment of ovariectomized rats indicates according to DEXA standards a severe osteoporotic bone status in vertebral bone. Nonetheless, dysfunctional bone anabolism and enhanced bone catabolism are observed. Alterations of bone extracellular matrix proteins that correlate to inferior mechanical stability and affected microstructure were noticed and suggest further investigation. Treatment with dexamethasone was also seen to affect insulin and osteopontin levels and thus osteoblast function and maturation. This described animal model presents a recapitulation of clinically obtained data from early phase glucocorticoid-induced osteoporosis observed in patients.     

The biomaterial-mediated healing of critical size bone defects in the ovariectomized rat

Summary

This study demonstrated an impaired biomaterial-mediated bone regeneration in a critical sized calvarial defect established within an ovariectomized rat model. Histological and microtomographic evidences were supported by an impaired osteoblastic gene expression and altered expression of estrogen receptors and adipogenic markers.

Introduction

This work aims to address the bone regeneration process in the ovariectomized rat model, by assessing a calvarial critical size defect implanted with a biocompatible bovine bone mineral graft.

Methods

Animals were randomly divided into two groups: Ovx (bilateral ovariectomy) and Sham (control surgery). Following 8 weeks, all animals were submitted to a surgical bicortical craniotomy (5-mm circular critical size defect), which was filled with a biocompatible mineral graft. Animals were euthanized at 1, 3, and 6 months following graft implantation (n?=?10), and results on the orthotopic bone regeneration process were blindly evaluated by radiographic, microtomographic, histological, histomorphometric, and gene expression techniques.

Results

In the attained model, in both Sham and Ovx groups, the bone regenerative process was found to occur in a slow-paced manner. Likewise, a qualitative evaluation of the microtomographic and histological analysis, as well as quantitative data from histomorphometric indexes, revealed reduced bone regeneration in Ovx animals, at the assayed time points. Significant differences were attained at the 3 and 6 months. Gene expression analysis revealed a reduced expression of osteoblastic-related genes and an altered expression of estrogen receptors and adipogenic markers, within the regenerating bone of Ovx animals.

Conclusions

Due to the similarities between the osteoporotic animal model and the human condition of postmenopausal osteoporosis, it might be relevant to consider the potential clinical implication of the osteoporotic condition in the biomaterial-mediated bone tissue healing/regeneration process.     

Fracture rate in patients with myasthenia gravis: the general practice research database

Summary

The aim of this study was to evaluate fracture risk after onset of myasthenia gravis using the UK General Practice Research Database. Overall fracture risk is not statistically increased compared with age- and gender-matched controls irrespective of glucocorticoid use, but was increased in those using antidepressants, anxiolytics or anticonvulsants.

Introduction

Myasthenia gravis (MG) is a neuromuscular disease which has been associated with an increased falls risk and glucocorticoid-induced osteoporosis, recognized determinants of increased fracture risk. The aim of this study was to evaluate the risk of fracture after onset of MG.

Methods

We conducted a retrospective cohort study using the UK General Practice Research Database (1987–2009). Each MG patient was matched by age, sex, calendar time and practice to up to six patients without a history of MG and we identified all fractures and those associated with osteoporosis.

Results

Compared to the control cohort, there was no statistically significant increased risk observed in patients with MG for any fracture (adjusted hazard ratio [AHR] 1.11; 95 % confidence interval [CI], 0.84–1.47) or osteoporotic fractures (AHR 0.98 [95 % CI 0.67–1.41]). Further, use of oral glucocorticoids up to a cumulative dose exceeding 5 g prednisolone equivalents did not increase risk of osteoporotic fracture (AHR 0.99 [95 % CI, 0.31–3.14]) compared with MG patients without glucocorticoid exposure. However, fracture risk was higher in patients with MG prescribed antidepressants (AHR 3.27 [95 % CI, 1.63–6.55]), anxiolytics (AHR 2.18 [95 % CI, 1.04–4.57]) and anticonvulsants (AHR 6.88 [95 % CI, 2.91–16.27]).

Conclusion

Overall risk of fracture in patients with MG is not statistically increased compared with age- and gender-matched controls irrespective of glucocorticoid use but was increased in those using antidepressants, anxiolytics or anticonvulsants. These findings have implications in strategies preserving bone health in patients with MG.     

Suppressive effects of 1,4-dihydroxy-2-naphthoic acid administration on bone resorption

Summary

The main component of the metabolic by-products of fermentation by Propionibacterium freudenreichii ET-3 is 1,4-dihydroxy-2-naphthoic acid (DHNA), which has a naphthoquinone skeleton, as in vitamin K2. This study showed that DHNA improved bone mass reduction with osteoporosis model mice caused by FK506.

Introduction

Growth of the intestinal bacterium Lactobacillus bifidus is specifically facilitated by DHNA. The present study used osteoporosis model mice to investigate the effects of DHNA on bone remodeling.

Methods

FK506, an immunosuppressant, was used to prepare osteoporosis model mice. Thirty mice were divided into three groups: FK group, FK+DHNA group, and control group. In the FK group, FK506 was administered to induce bone mass reduction. In the FK-DHNA group, FK506 and DHNA were administered concurrently to observe improvements in bone mass reduction. To ascertain systemic and local effects of DHNA, we investigated systemic pathological changes in colon, kidney function and cytokine dynamics, and morphological and organic changes in bone and osteoclast dynamics as assessed by culture experiments.

Results

Compared to the FK group without DHNA, colon damage and kidney dysfunction were milder for FK+DHNA group, and production of inflammatory cytokines (interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α) was more suppressed. Furthermore, compared to the group without DHNA, histological analyses and radiography showed that bone resorption was suppressed for the DHNA group. Culture experiments using osteoclasts from murine bone marrow showed osteoclast suppression for the DHNA group compared to the group without DHNA.

Conclusion

These results show that DHNA has some effects for improving bone mass reduction caused by FK506.     

FRAX® assessment of osteoporotic fracture probability in Switzerland

Summary

A Swiss-specific FRAX® model was developed. Patient profiles at increased probability of fracture beyond currently accepted reimbursement thresholds for bone mineral density (BMD) measurement by dual X-ray absorptiometry (DXA), and osteoporosis treatment were identified.

Introduction

This study aimed to determine which constellations of clinical risk factors, alone, or combined with BMD measurement by DXA, contribute to improved identification of Swiss patients with increased probability of fracture.

Methods

The 10-year probability of hip and any major osteoporotic fracture was computed for both sexes, based on Swiss epidemiological data, integrating fracture risk and death hazard, in relation to validated clinical risk factors, with and without BMD values.

Results

Fracture probability increased with age, lower body mass index (BMI), decreasing BMD T-score, and all clinical risk factors used alone or combined. Several constellations of risk factor profiles were identified, indicating identical or higher absolute fracture probability than risk factors currently accepted for DXA reimbursement in Switzerland. With identical sex, age and BMI, subjects with parental history of hip fracture had as high a probability of any major osteoporotic fracture as patients on oral glucocorticoids or with a prevalent fragility fracture. The presence of additional risk factors further increased fracture probability.

Conclusions

The customised FRAX® model indicates that a shift from the current DXA-based intervention paradigm, toward a fracture risk continuum based on the 10-year probability of any major osteoporotic fracture may improve identification of patients at increased fracture risk.     

Biochemische Knochenresorptionsmarker in der Heilungsphase osteoporotischer Frakturen

Background

This study investigated the progression and clinical relevance of biochemical resorption marker values during fracture healing in osteoporosis.

Patients and methods

In 44 patients with distal radius fractures and 29 patients without fractures, the blood and urine concentrations of pyridinoline (PYD), deoxypyridinoline (DPD), N-telopeptides (NTx), and bone sialoprotein (BSP) were recorded on the day of trauma as well as during further progression. All postmenopausal patients underwent bone density measurement. Accordingly, patients were divided into premenopausal, postmenopausal osteoporotic, and postmenopausal nonosteoporotic groups.

Results

Between the groups, PYD, DPD, and NTx showed significant differences in their initial values. However, their further relative progression was primarily affected by the chosen therapy.

Conclusion

Bone resorption markers can diagnostically point to osteoporosis and are significant parameters in fracture healing.     

Chlamydia pneumoniae and osteoporosis-associated bone loss: a new risk factor?

Summary

We found an association between the presence of Chlamydia pneumoniae DNA both in osteoporotic bone tissue and peripheral blood mononuclear cells (PBMCs) and the increase in circulating resorptive cytokines.

Introduction

Our study was designed to determine whether C. pneumoniae infection may be involved in osteoporosis-associated bone loss.

Methods

The study included 59 women undergoing hip joint replacement surgery for femoral neck fracture: 32 with osteoporosis and 27 with osteoarthritis. A total of 118 tissue specimens (59 bone tissues, 59 PBMCs) were examined for C. pneumoniae DNA by real-time polymerase chain reaction (PCR). Serum levels of soluble receptor activator of nuclear factor kappa B ligand (sRANKL), osteoprotegerin (OPG), interleukin (IL)-1β, tumor necrosis factor-α, and IL-6 were also measured.

Results

C. pneumoniae DNA was detected in osteoporotic bone tissue whereas it was not found in non-osteoporotic bone tissue (p?<?0.05). A significantly higher rate of C. pneumoniae DNA (p?<?0.05) was found in PBMCs of osteoporotic patients than in those of osteoarthritis patients. Among osteoporotic patients, serum sRANKL, IL-1, and IL-6 concentrations as well as sRANKL/OPG ratio significantly differ between patients with bone tissue and PBMCs positive to C. pneumoniae and C. pneumoniae-negative patients.

Conclusion

The association between the presence of C. pneumoniae DNA, both in bone tissue and PBMCs, and the increase in sRANKL/OPG ratio as well as in IL-1β and IL-6 levels observed in osteoporotic patients suggests C. pneumoniae infection as a new risk factor for osteoporosis.     

Oleuropein enhances osteoblastogenesis and inhibits adipogenesis: the effect on differentiation in stem cells derived from bone marrow

Summary

The effects of oleuropein on the processes of osteoblastogenesis and adipogenesis in mesenchymal stem cells (MSCs) from human bone marrow have been studied. We report that oleuropein, a polyphenol abundant in olive tree products, reduces the expression of peroxisome proliferator-activated receptor gamma (PPARγ), inhibits adipocyte differentiation, and enhances differentiation into osteoblast.

Introduction

Age-related bone loss is associated with osteoblast insufficiency during continuous bone remodeling. It has been suggested that the formation of osteoblasts in bone marrow is closely associated with adipogenesis, and age-related changes in this relationship could be responsible for the progressive adiposity of bone marrow which occurs with osteoporosis. In addition, the consumption of oleuropein, a major polyphenol in olive leaves and olive oil, has been associated with a reduction in bone loss.

Methods

We have analyzed the effects of oleuropein—at concentrations between 10^?6 and 10^?4 M—on the processes of osteoblastogenesis and adipogenesis in MSCs from human bone marrow.

Results

The results show an increase in osteoblast differentiation and a decrease in adipocyte differentiation when there is oleuropein in the culture media. The gene expression of osteoblastogenesis markers, RUNXII, osterix, collagen type I, osteocalcin, or alkaline phosphatase (ALP), was higher in osteoblast-induced oleuropein-treated cells. Also, the ALP activity and extracellular matrix mineralization were higher when oleuropein was present in the media. Oleuropein in MSCs induced adipocytes to produce a decrease in the expression of the genes involved in adipogenesis, the PPARγ, lipoprotein lipase, or fatty acid-binding protein 4, and minor fat accumulation.

Conclusion

Our data suggest that oleuropein, highly abundant in olive tree products included in the traditional Mediterranean diet, could prevent age-related bone loss and osteoporosis.     

Too Fit To Fracture: exercise recommendations for individuals with osteoporosis or osteoporotic vertebral fracture

Summary

A consensus process was conducted to develop exercise recommendations for individuals with osteoporosis or vertebral fractures. A multicomponent exercise program that includes balance and resistance training is recommended.

Introduction

The aim was to develop consensus on exercise recommendations for older adults: (1) with osteoporosis and (2) with osteoporotic vertebral fracture(s).

Methods

The Grading of Recommendations Assessment, Development, and Evaluation method was used to evaluate the quality of evidence and develop recommendations. Outcomes important for decision making were nominated by an expert panel and patient advocates. They included falls, fractures, bone mineral density (BMD), and adverse events for individuals with osteoporosis/vertebral fractures, and pain, quality of life, and function for those with vertebral fracture. Meta-analyses evaluating the effects of exercise on the outcomes were reviewed. Observational studies or clinical trials were reviewed when meta-analyses were not available. Quality ratings were generated, and informed the recommendations.

Results

The outcome for which evidence is strongest is falls. Point estimates of the effects of exercise on falls, fractures, and BMD vary according to exercise type. There is not enough evidence to quantify the risks of exercise in those with osteoporosis or vertebral fracture. Few trials of exercise exist in those with vertebral fracture. The exercise recommendations for exercise in individuals with osteoporosis or osteoporotic vertebral fracture are conditional. The panel strongly recommends a multicomponent exercise program including resistance and balance training for individuals with osteoporosis or osteoporotic vertebral fracture. The panel recommends that older adults with osteoporosis or vertebral fracture do not engage in aerobic training to the exclusion of resistance or balance training.

Conclusions

The consensus of our international panel is that exercise is recommended for older adults with osteoporosis or vertebral fracture, but our recommendations are conditional.     

Effects of cyclosporine on bone mineral density in patients with glucocorticoid-dependent nephrotic syndrome in remission

Purpose

Cyclosporine (CsA) is often prescribed to patients with glucocorticoid (GC)-dependent nephrotic syndrome. Although it is well known that long-term administration of GC causes osteoporosis, the effects of CsA on bone metabolism are not fully established. Therefore, we examined the effects of CsA on bone metabolism in patients with GC-dependent nephrotic syndrome in remission.

Methods

We followed 23 patients treated with prednisolone alone (GC alone group) and 17 patients treated with CsA in combination with prednisolone (GC + CsA group). Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry, and biochemical markers of bone metabolism were simultaneously measured in serum and urine samples.

Results

BMD decreased significantly in the GC group from 752 to 623 mg/cm² but non-significantly in the GC + CsA group from 751 to 684 mg/cm². Although the cumulative dose of GC increased in both groups, there were no significant differences in biochemical markers at either the start or the end of the study. Vertebrate bone fracture and other side effects associated with CsA treatment did not occur in our study.

Conclusions

Our results indicate that CsA does not accelerate GC-induced osteoporosis in patients with nephrotic syndrome. We conclude that CsA is appropriate for the treatment of GC-dependent nephrotic syndrome, because it does not adversely affect bone metabolism and has favorable glomerular effects.     

The association between osteoporosis and static balance in elderly women

Summary

This study aimed at answering the question: do people with high bone loss have greater postural instability? Groups were separated into group 1: women with normal bone mineral density, group 2: women with osteopenia, and group 3: women with osteoporosis. The balance was evaluated in four upright postural situations. Osteoporosis group had greater oscillation in the anteroposterior displacement in all situations compared to control group and the greatest mediolateral displacement in all situations compared to other groups.

Introduction

It is not known whether the presence of osteoporosis can be considered a factor aggravating the postural control. This study aimed at answering the question: do people with high bone loss have greater postural instability?

Methods

This study was divided into three groups: group 1 (n?=?20) consisting of women with normal bone mineral density, group 2 (n?=?20) women with osteopenia, and group 3 (n?=?20) women with osteoporosis. All the participants were submitted to evaluation of the balance using the Polhemus system in four upright postural situations.

Results

Osteoporosis group had greater oscillation in the anteroposterior displacement in all situations compared to control group. The osteoporosis group also showed the greatest mediolateral displacement in all situations compared to other groups.

Conclusion

The results suggest that osteoporotic women had the worst balance, possibly due to the more pronounced body changes compared to non-osteoporotic women.