Journal of Osteoporosis

Dropouts and Compliance in Exercise Interventions Targeting Bone Mineral Density in Adults: A Meta-Analysis of Randomized Controlled Trials

George A. Kelley and Kristi S. Kelley — Mon, 03 Jun 2013 15:56:39 +0000

Background. Dropouts and compliance to exercise interventions targeting bone mineral density (BMD) in adults are not well established. The purpose of this study was to address that gap. Methods. Meta-analysis of randomized controlled exercise intervention trials in adults ≥18 years of age. The primary outcomes were dropouts in the exercise and control groups as well as compliance to the exercise interventions. A random-effects model was used to pool results. Moderator analyses were conducted using mixed-effects ANOVA-like models and metaregression. Statistical significance was set at . Results. Thirty-six studies representing 3,297 participants (1,855 exercise, 1,442 control) were included. Dropout rates in the exercise and control groups averaged 20.9% (95% CI 16.7%–25.9%) and 15.9% (11.8%–21.1%) while compliance to exercise was 76.3% (71.7%–80.3%). For both exercise and control groups, greater dropout rates were associated with studies conducted in the USA versus other countries, females versus males, premenopausal versus postmenopausal women, younger versus older participants, longer studies (controls only), and high- versus moderate-intensity training (exercisers only). Greater compliance to exercise was associated with being female, home- or facility-based exercise versus both, and shorter studies. Conclusion. These findings provide important information for researchers and practitioners with respect to exercise programs targeting BMD in adults.

Women’s Attitudes and Health Beliefs toward Osteoporosis Screening in a Community Pharmacy

Priyanka Deo, Rajesh Nayak, and Jigar Rajpura — Tue, 28 May 2013 08:54:12 +0000

The aim of this study was to examine women’s attitudes and health beliefs towards osteoporosis screening in a community pharmacy setting, utilizing the theoretical framework of Health Belief Model. A nonexperimental, cross-sectional research design, examining a convenience sample of women aged 18 and over, from several New York City senior care centers, a church, and a university campus in New York, was employed to assess the study objectives. Osteoporosis Health Belief Scale questionnaire was used to study the attitudes and health beliefs of participants towards bone mineral density screening in community pharmacy. From the study, it was observed that perceptions of severity and susceptibility towards osteoporosis and subjects’ demographic characteristics did not seem to significantly influence the decision to screen in a community pharmacy setting. The perceptions of benefits of community pharmacy-based osteoporosis screening and the perceived barriers were found to be of greater importance in women’s decisions to engage in osteoporosis-specific preventive behavior.

High Folic Acid Intake during Pregnancy Lowers Body Weight and Reduces Femoral Area and Strength in Female Rat Offspring

Mon, 27 May 2013 16:33:59 +0000

Rats fed gestational diets high in multivitamin or folate produce offspring of altered phenotypes. We hypothesized that female rat offspring born to dams fed a gestational diet high in folic acid (HFol) have compromised bone health and that feeding the offspring the same HFol diet attenuates these effects. Pregnant rats were fed diets with either recommended folic acid (RFol) or 10-fold higher folic acid (HFol) amounts. Female offspring were weaned to either the RFol or HFol diet for 17 weeks. HFol maternal diet resulted in lower offspring body weights (6%, ) and, after adjusting for body weight and femoral length, smaller femoral area (2%, ), compared to control diet. After adjustments, HFol pup diet resulted in lower mineral content (7%, ) and density (4%, ) of lumbar vertebra 4 without differences in strength. An interaction between folate content of the dam and pup diets revealed that a mismatch resulted in lower femoral peak load strength () and stiffness (). However, the match in folate content failed to prevent lower weight gain. In conclusion, HFol diets fed to rat dams and their offspring affect area and strength of femurs and mineral quantity but not strength of lumbar vertebrae in the offspring.

Purinergic Signaling in Bone

Niklas Rye Jørgensen, Elena Adinolfi, Isabel Orriss, and Peter Schwarz — Thu, 16 May 2013 15:19:05 +0000

A Study of Bone Mineral Density and Its Determinants in Type 1 Diabetes Mellitus

Ameya Joshi, Premlata Varthakavi, Manoj Chadha, and Nikhil Bhagwat — Sun, 31 Mar 2013 13:26:18 +0000

Type 1 diabetes mellitus (T1DM) has been inconsistently associated with low bone mineral density (BMD) and increased fracture risk. 86 consecutive T1DM cases and 140 unrelated age and sex matched healthy nondiabetic controls were included in the study. After history and examination, BMD and body composition were assessed by dual energy X-ray absorptiometry (DXA). Serum samples were analyzed for calcium, phosphorus, albumin, creatinine, alkaline phosphatase, 25 (OH) vitamin D3, intact parathormone (PTH) levels (both cases and controls) and HbA1c, antimicrosomal and IgA tissue transglutaminase (IgA TTG) antibodies, cortisol, follicle stimulating hormone (FSH), testosterone, sex hormone binding globulin (SHBG), tetraiodothyronine (T4), thyroid stimulating hormone (TSH), growth hormone (GH), insulin-like growth factor-1 (IGF-1), and insulin-like growth factor binding protein 3 (IGFBP3) (cases only). T1DM cases had a lower BMD as compared to controls at both total body (TB) and lumbar spine (LS) (). Patients with celiac autoimmunity (CA) had significantly, lower BMD as compared to age, sex, and body mass index (BMI) matched T1DM controls. Linear regression analysis showed that low BMD in T1DM patients was associated with poor glycaemic control, lower IGF-1 levels, less physical activity (in total population as well as in male and female subgroups), and lower body fat percentage (in females) and higher alkaline phosphatase level (in males) ().

Osteoporosis Self-Assessment Tool Performance in a Large Sample of Postmenopausal Women of Mendoza, Argentina

Fernando D. Saraví — Mon, 04 Mar 2013 16:15:15 +0000

The Osteoporosis Self-assessment Tool (OST) is a clinical instrument designed to select patients at risk of osteoporosis, who would benefit from a bone mineral density measurement. The OST only takes into account the age and weight of the subject. It was developed for Asian women and later validated for European and North American white women. The performance of the OST in a sample of 4343 women from Greater Mendoza, a large metropolitan area of Argentina, was assessed. Dual X-ray absorptiometry (DXA) scans of lumbar spine and hip were obtained. Patients were classified as either osteoporotic () or nonosteoporotic () according to their lowest T-score at any site. Osteoporotic patients had lower OST scores (). A receiver operating characteristic (ROC) curve showed an area under the curve of 71% (), with a sensitivity of 83.7% and a specificity of 44% for a cut-off value of 2. Positive predictive value was 52% and negative predictive value was 79%. The odds ratio for the diagnosis of osteoporosis was 4.06 (CI95 3.51 to 4.71; ). It is concluded that the OST is useful for selecting postmenopausal women for DXA testing in the studied population.

Bone Mineral Density and Body Composition of Adult Premenopausal Women with Three Levels of Physical Activity

Fernando D. Saraví and Fabiana Sayegh — Mon, 25 Feb 2013 11:14:25 +0000

Weight-bearing and resistance physical activities are recommended for osteoporosis prevention, but it is unclear whether an intensity level above current recommendations has a positive effect on adult premenopausal women. Body composition and bone mineral density (BMD) by DXA were compared in three groups of women as follows: Sedentary, Maintenance exercise, and federated Sport Team ( for each group). Physical activity was estimated from the International Physical Activity Questionnaire (IPAQ). The groups did not differ in age, height, weight, or body mass index. Bone mineral content and non-fat soft tissue mass were higher and fat mass was lower in the Sport Team group than in the other groups. The same was true for BMD of total skeleton, lumbar spine, femoral neck, and total hip. A test for linear trend of body composition and BMD showed significant results when including all three groups. Simple and multiple regression analyses showed significant associations between physical activity level (or alternatively, years of participation in programmed physical activity) and bone mass measures at all sites except for the middle third of radius. It is concluded that a level of physical activity higher than that usually recommended benefits bone health in adult premenopausal women.

Comparative Evaluation of Enalapril and Losartan in Pharmacological Correction of Experimental Osteoporosis and Fractures of Its Background

Wed, 16 Jan 2013 14:33:06 +0000

In the experiment on the white Wistar female rats (222 animals), the osteoprotective effect of enalapril and losartan was studied on experimental models of osteoporosis and osteoporotic fractures. It was revealed that in rats after ovariectomy, the endothelial dysfunction of microcirculation vessels of osteal tissue develops, resulting in occurrence of osteoporosis and delay of consolidation of experimental fractures. Enalapril and losartan prevented the reduction of microcirculation in bone, which was reflected in slowing the thinning of bone trabeculae and in preventing the occurrence of these microfractures, as well as increasing quality of experimental fractures healing.

Evaluation of Clinical Decision Rules for Bone Mineral Density Testing among White Women

Michael E. Anders, Lori Turner, and Jeanne Freeman — Thu, 10 Jan 2013 14:57:41 +0000

Background. Osteoporosis is a devastating, insidious disease that causes skeletal fragility. Half of women will suffer osteoporotic fractures during their lifetimes. Many fractures occur needlessly, because of inattentiveness to assessment, diagnosis, prevention, and treatment of osteoporosis. Study Purpose. Study Purpose. To evaluate the discriminatory performance of clinical decision rules to determine the need to undergo bone mineral density testing. Methods. A nationally representative sample from the Third National Health and Nutrition Examination Survey consisted of 14,060 subjects who completed surveys, physical examinations, laboratory tests, and bone mineral density exams. Multivariable linear regression tested the correlation of covariates that composed the clinical decision rules with bone mineral density. Results. Increased age and decreased weight were variables in the final regression models for each gender and race/ethnicity. Among the indices, the Osteoporosis Self-Assessment Tool, which is composed of age and weight, performed best for White women. Study Implications. These results have implications for the prevention, assessment, diagnosis, and treatment of osteoporosis. The Osteoporosis Self-Assessment Tool performed best and is inexpensive and the least time consuming to implement.

Detecting Early Biomechanical Effects of Zoledronic Acid on Femurs of Osteoporotic Female Rats

Tue, 04 Dec 2012 12:05:30 +0000

Aim. To investigate the biomechanical effects of zoledronic acid (ZA) on femurs of female osteoporotic rats after follow-up periods of 9 and 12 months. Methods. Eighty female Wistar rats were prospectively assessed. At 60 days of age, the animals were randomly divided into two groups: bilateral oophorectomy (O) () and sham surgery (S) (). At 90 days of age, groups O and S were randomly subdivided into four groups, according to whether 0.1 mg/kg of ZA or distilled water (DW) was intraperitoneally administered: OZA (), ODW (), SZA (), and SDW (). The animals were sacrificed at 9 and 12 months after the administration of the substances, and then their right femurs were removed and analyzed biomechanically. Axial compression tests that focused on determining the maximum load (N), yield point (N), and stiffness coefficient (N/mm) of the proximal femur were performed in the biomechanical study. Results. ZA significantly increased the maximum load and yield point, reducing the stiffness coefficient concerning the oophorectomy status and follow-up period. Conclusion. Zoledronic acid, at a dose of 0.1 mg/kg, significantly increased the maximum loads and yield points and reduced the stiffness coefficients in the femurs of female rats with osteoporosis caused by bilateral oophorectomy.

Divergent Significance of Bone Mineral Density Changes in Aging Depending on Sites and Sex Revealed through Separate Analyses of Bone Mineral Content and Area

Sun, 25 Nov 2012 08:46:12 +0000

Bone mineral density (aBMD) is equivalent to bone mineral content (BMC) divided by area. We rechecked the significance of aBMD changes in aging by examining BMC and area separately. Subjects were 1167 community-dwelling Japanese men and women, aged 40–79 years. ABMDs of femoral neck and lumbar spine were assessed by DXA twice, at 6-year intervals. The change rates of BMC and area, as well as aBMD, were calculated and described separately by the age stratum and by sex. In the femoral neck region, aBMDs were significantly decreased in all age strata by an increase in area as well as BMC loss in the same pattern in both sexes. In the lumbar spine region, aBMDs decreased until the age of 60 in women, caused by the significant BMC decrease accompanying the small area change. Very differently in men, aBMDs increased after their 50s due to BMC increase, accompanied by an area increase. Separate analyses of BMC and area change revealed that the significance of aBMD changes in aging was very divergent among sites and between sexes. This may explain in part the dissociation of aBMD change and bone strength, suggesting that we should be more cautious when interpreting the meaning of aBMD change.

Osteoporosis Knowledge of Students in Relevant Healthcare Academic Programs

Vu H. Nguyen and Ze Wang — Mon, 19 Nov 2012 12:44:12 +0000

For healthcare professionals who treat individuals with osteoporosis, it is vital that they receive adequate education on osteoporosis to ensure sufficient knowledge of osteoporosis to properly treat individuals with the disease. To test for adequate osteoporosis education, a study was conducted to measure osteoporosis knowledge in 206 students in relevant healthcare academic programs, such as nursing, pharmacy, physical therapy, and dietetics. The study showed that differences existed in osteoporosis knowledge in general between the programs and between different years of students in the same programs. There were also discrepancies in specific areas of osteoporosis knowledge between the classes of students, and the average scores of correctly answered items were only as high as 24.40 (76.3%) out of 32 items on osteoporosis knowledge. This study shows that students have osteoporosis knowledge and that it is not completely inadequate; however, osteoporosis knowledge could still be more sufficient, and results demonstrate the need to increase osteoporosis education in the curriculum for these healthcare academic programs to increase osteoporosis knowledge and better prepare graduates and professionals to treat individuals with the disease.

Survivorship and Severe Complications Are Worse for Octogenarians and Elderly Patients with Pelvis Fractures as Compared to Adults: Data from the National Trauma Data Bank

Amir Matityahu, Joshua Elson, Saam Morshed, and Meir Marmor — Wed, 07 Nov 2012 09:39:28 +0000

Purpose. This study examined whether octogenarians and elderly patients with pelvic fractures have a different risk of complication and mortality as compared to adults. Methods. Data was gathered from the National Trauma Data Bank from 2002 to 2006. There were 32,660 patients 18–65, 6,408 patients 65–79, and 5,647 patients ≥ 80 years old with pelvic fractures. Descriptive statistics and bivariate and multivariate analyses were performed with the adult population as a referent. Results. Multivariate analysis showed 4.7-fold higher odds of death and 4.57 odds of complications in the octogenarian group after a pelvic fracture compared to adults. The elderly had 1.81-fold higher odds of death and 2.18-fold higher odds of severe complications after sustaining a severe pelvic fracture relative to adults. An ISS ≥ 16 yielded 15.1-fold increased odds of mortality and 18.3-fold higher odds of severe complications. Hypovolemic shock had 7.65-fold increased odds of death and 6.31-fold higher odds of severe complications. Between the ages of 18 and 89 years, there is approximately a 1% decrease in survivorship every 10 years. Conclusions. This study illustrates that patients older than 80 years old with pelvis fractures have a higher mortality and complications rate than elderly or adult patients.

Effects of Kalsis, A Dietary Supplement, on Bone Metabolism in the Ovariectomized Rats

Thu, 04 Oct 2012 13:20:40 +0000

We studied the ability of Kalsis, a food supplement that contains selenium, citric acid, and vitamin E, to prevent the effects of ovariectomy on bone loss. Six-month-old, Wistar female rats were studied. Groups (): SHAM: sham-operated rats; OVX: ovariectomized rats, treated with vehicle; OVX + Kalsis: ovariectomized rats treated with Kalsis (25 mg/kg/day) for 3 months. Bone mineral density (BMD) was determined by DXA in lumbar spine and femur. Computerized microtomography (CT) in femur and serum osteocalcin (BGP), aminoterminal propeptide of procollagen I (PINP), β-isomer of carboxyterminal telopeptide of collagen I (CTX), and 5b isoenzyme of tartrate-resistant acid phosphatase (TRAP) were performed. Treatment with Kalsis prevented BMD loss in OVX group. CT showed a decrease in BV/TV, and trabecular number, and an increase in trabecular separation in OVX rats. Kalsis administration attenuated partially bone loss observed by CT due to ovariectomy. BGP, PINP, and the resorption index (CTX/TRAP) were increased in OVX group. Treatment with Kalsis maintained this increase. The mechanism of action of this supplement is not through a decrease in bone remodelling rate. The antioxidant action of this food supplement, due to the synergism of all its components, as a cause of its beneficial effect is suggested.

The Role of Purinergic Receptors in Cancer-Induced Bone Pain

Sarah Falk, Maria Uldall, and Anne-Marie Heegaard — Wed, 03 Oct 2012 10:36:15 +0000

Cancer-induced bone pain severely compromises the quality of life of many patients suffering from bone metastasis, as current therapies leave some patients with inadequate pain relief. The recent development of specific animal models has increased the understanding of the molecular and cellular mechanisms underlying cancer-induced bone pain including the involvement of ATP and the purinergic receptors in the progression of the pain state. In nociception, ATP acts as an extracellular messenger to transmit sensory information both at the peripheral site of tissue damage and in the spinal cord. Several of the purinergic receptors have been shown to be important for the development and maintenance of neuropathic and inflammatory pain, and studies have demonstrated the importance of both peripheral and central mechanisms. We here provide an overview of the current literature on the role of purinergic receptors in cancer-induced bone pain with emphasis on some of the difficulties related to studying this complex pain state.

Osteoporotic Characteristics Persist in the Spine of Ovariectomized Sheep after Withdrawal of Corticosteroid Administration

Tue, 02 Oct 2012 11:09:25 +0000

A validated ovine model of osteoporosis achieves severe bone loss in a relatively short period. This study investigated if osteoporotic features persist in this model after cessation of corticosteroid administration. Methods. Osteoporosis was induced in nine ewes by chronic corticosteroid injection, ovariectomy, and low calcium diet. Six ewes were used as controls. Bone mineral density (BMD) of the lumbar spine (LS) and body weight were assessed at regular intervals. After five months, corticosteroid treatment was withdrawn systematically over one month. Three months later, all animals were euthanised, and the LS was collected for histomorphometric analysis. Results. BMD in the LS of osteoporotic sheep was 25% lower than control sheep. Body weight of osteoporotic sheep was reduced in the first month of the corticosteroid withdrawal period but returned to baseline level thereafter. Trabecular bone volume of LS in osteoporotic sheep was 27% lower than controls and showed a heterogeneous structure. Conclusions. Osteoporotic characteristics remain in the vertebra after ceasing corticosteroid administration providing an opportunity to evaluate potential systemic or local treatments in vivo under realistic physiological conditions. The microstructural arrangement of vertebral trabecular bone in sheep is similar to humans demonstrating further relevance of this model for preclinical investigations.

Normative Data for Bone Mass in Healthy Term Infants from Birth to 1 Year of Age

Sina Gallo, Catherine A. Vanstone, and Hope A. Weiler — Tue, 02 Oct 2012 10:07:53 +0000

For over 2 decades, dual-energy X-ray absorptiometry (DXA) has been the gold standard for estimating bone mineral density (BMD) and facture risk in adults. More recently DXA has been used to evaluate BMD in pediatrics. However, BMD is usually assessed against reference data for which none currently exists in infancy. A prospective study was conducted to assess bone mass of term infants (37 to 42 weeks of gestation), weight appropriate for gestational age, and born to healthy mothers. The group consisted of 33 boys and 26 girls recruited from the Winnipeg Health Sciences Center (Manitoba, Canada). Whole body (WB) as well as regional sites of the lumbar spine (LS 1–4) and femur was measured using DXA (QDR 4500A, Hologic Inc.) providing bone mineral content (BMC) for all sites and BMD for spine. During the year, WB BMC increased by 200% ( versus g), spine BMC by 130% ( versus g), and femur BMC by 190% ( versus g). Spine BMD increased by 14% ( versus g/cm2) during the year. This data, representing the accretion of bone mass during the first year of life, is based on a representative sample of infants and will aid in the interpretation of diagnostic DXA scans by researchers and health professionals.

Bone Mineral Density in Spinal Cord Injury: An Evaluation of the Distal Femur

Alexandra Passos Gaspar, Marise Lazaretti-Castro, and Cynthia M. A. Brandão — Tue, 28 Aug 2012 09:14:34 +0000

Osteoporosis (OP) in spinal cord injury (SCI) patients is a secondary process in which numerous factors are involved. Diagnosing OP and the threshold for fractures in this population, based on bone mineral density (BMD) measured by double energy X-ray absorptiometry (DXA), is still a challenge. The aim of this study was to evaluate bone mineral loss by DXA, its relationship with body composition and fracture incidence, in complete paraplegics patients, compared with aged-matched controls; we include a nonstandard bone site, the distal femur, and describe the technical and practical aspects of this procedure. Twenty-five SCI patients were included in the study and 17 subjects as control group. No prior or recent fractures were observed in X-ray analysis. The BMD of all femoral sites was significantly lower in patients than in controls (femoral neck, total femur, and distal femur); no difference was observed between BMD of the lumbar spine of patients and controls. We found inverse relationship between time of SCI and bone mineral mass only for distal femur BMD. We conclude that the distal femur is a more sensitive bone site for assessing bone loss by DXA, in SCI patients, than the proximal femoral sites.

P2X7 Receptor Function in Bone-Related Cancer

Elena Adinolfi, Francesca Amoroso, and Anna Lisa Giuliani — Thu, 16 Aug 2012 11:20:03 +0000

Modulation of tumor microenvironment by different mediators is central in determining neoplastic formation and progression. Among these molecules extracellular ATP is emerging as a good candidate in promoting cell growth, neovascularization, tumor-host interactions, and metastatization. This paper summarizes recent findings on expression and function of P2X7 receptor for extracellular ATP in primary and metastatic bone cancers. Search of mRNA expression microchip databases and literature analysis demonstrate a high expression of P2X7 in primary bone tumors as well as in other malignancies such as multiple myeloma, neuroblastoma, breast, and prostate cancer. Evidence that P2X7 triggers NFATc1, PI3K/Akt, ROCK, and VEGF pathways in osteoblasts promoting either primary tumor development or osteoblastic lesions is also reported. Moreover, P2X7 receptor is involved in osteoclast differentiation, RANKL expression, matrix metalloproteases and cathepsin secretion thus promoting bone resorption and osteolytic lesions. Taken together these data point to a pivotal role for the P2X7 receptor in bone cancer biology.

Potential Extensions of the US FRAX Algorithm

Wed, 15 Aug 2012 09:03:33 +0000

To determine if the revised US FRAX can identify those at high risk for fractures at any skeletal site, we studied 250 women and 249 men ≥40 years old from an age-stratified random sample of Rochester, MN residents. At baseline, femoral neck (FN) bone density was assessed, as were the clinical risk factors included in FRAX, along with additional fracture risk factors such as bone turnover markers and fall history. Fracture ascertainment through periodic interviews and comprehensive medical record review was performed over 10 years of followup. In both women and men, a higher FRAX probability at baseline was associated with greater subsequent likelihood of a major osteoporotic fracture. However, a relative 10% increase in the FRAX 10-year fracture probability was also associated with a 1.4-fold increase (95% confidence interval (CI) 1.1–1.7) in other fractures in women and a 1.7-fold increase (95% CI 0.8–3.1) in men. Furthermore, FRAX predicted asymptomatic vertebral fractures and fractures generally in both sexes. The addition of risk factors not currently included in FRAX did not appear to improve the accuracy of fracture risk prediction. FRAX may provide a conservative estimate of risk for major osteoporotic fractures, but it also predicts fractures generally.

Genetic Background Strongly Influences the Bone Phenotype of P2X7 Receptor Knockout Mice

Thu, 09 Aug 2012 16:07:57 +0000

The purinergic P2X7 receptor is expressed by bone cells and has been shown to be important in both bone formation and bone resorption. In this study we investigated the importance of the genetic background of the mouse strains on which the P2X7 knock-out models were based by comparing bone status of a new BALB/cJ P2X7−/− strain with a previous one based on the C57BL/6 strain. Female four-month-old mice from both strains were DXA scanned on a PIXImus densitometer; femurs were collected for bone strength measurements and serum for bone marker analysis. Bone-related parameters that were altered only slightly in the B6 P2X7−/− became significantly altered in the BALB/cJ P2X7−/− when compared to their wild type littermates. The BALB/cJ P2X7−/− showed reduced levels of serum C-telopeptide fragment (s-CTX), higher bone mineral density, and increased bone strength compared to the wild type littermates. In conclusion, we have shown that the genetic background of P2X7−/− mice strongly influences the bone phenotype of the P2X7−/− mice and that P2X7 has a more significant regulatory role in bone remodeling than found in previous studies.

Association between P2X7 Receptor Polymorphisms and Bone Status in Mice

Sun, 05 Aug 2012 08:57:27 +0000

Macrophages from mouse strains with the naturally occurring mutation P451L in the purinergic receptor P2X7 have impaired responses to agonists (1). Because P2X7 receptors are expressed in bone cells and are implicated in bone physiology, we asked whether strains with the P451L mutation have a different bone phenotype. By sequencing the most common strains of inbred mice, we found that only a few strains (BALB, NOD, NZW, and 129) were harboring the wild allelic version of the mutation (P451) in the gene for the purinergic receptor P2X7. The strains were compared by means of dual energy X-ray absorptiometry (DXA), bone markers, and three-point bending. Cultured osteoclasts were used in the ATP-induced pore formation assay. We found that strains with the P451 allele (BALB/cJ and 129X1/SvJ) had stronger femurs and higher levels of the bone resorption marker C-telopeptide collagen (CTX) compared to C57Bl/6 (B6) and DBA/2J mice. In strains with the 451L allele, pore-formation activity in osteoclasts in vitro was lower after application of ATP. In conclusion, two strains with the 451L allele of the naturally occurring mutation P451L, have weaker bones and lower levels of CTX, suggesting lower resorption levels in these animals, which could be related to the decreased ATP-induced pore formation observed in vitro. The importance of these findings for the interpretation of the earlier reported effects of P2X7 in mice is discussed, along with strategies in developing a murine model for testing the therapeutic effects of P2X7 agonists and antagonists upon postmenopausal osteoporosis.

Modulating P2X7 Receptor Signaling during Rheumatoid Arthritis: New Therapeutic Approaches for Bisphosphonates

Alberto Baroja-Mazo and Pablo Pelegrín — Sun, 08 Jul 2012 11:17:34 +0000

P2X7 receptor-mediated purinergic signaling is a well-known mechanism involved in bone remodeling. The P2X7 receptor has been implicated in the pathophysiology of various bone and cartilage diseases, including rheumatoid arthritis (RA), a widespread and complex chronic inflammatory disorder. The P2X7 receptor induces the release into the synovial fluid of the proinflammatory factors (e.g., interleukin-1β, prostaglandins, and proteases) responsible for the clinical symptoms of RA. Thus, the P2X7 receptor is emerging as a novel anti-inflammatory therapeutic target, and various selective P2X7 receptor antagonists are under clinical trials. Extracellular ATP signaling acting through the P2X7 receptor is a complex and dynamic scenario, which varies over the course of inflammation. This signaling is partially modulated by the activity of ectonucleotidases, which degrade extracellular ATP to generate other active molecules such as adenosine or pyrophosphates. Recent evidence suggests differential extracellular metabolism of ATP during the resolution of inflammation to generate pyrophosphates. Extracellular pyrophosphate dampens proinflammatory signaling by promoting alternative macrophage activation. Our paper shows that bisphosphonates are metabolically stable pyrophosphate analogues that are able to mimic the anti-inflammatory function of pyrophosphates. Bisphosphonates are arising per se as promising anti-inflammatory drugs to treat RA, and this therapy could be improved when administrated in combination with P2X7 receptor antagonists.

Bone Mineral Density of Adolescent Female Tennis Players and Nontennis Players

Kevser Ermin, Scott Owens, M. Allison Ford, and Martha Bass — Sun, 01 Jul 2012 15:51:03 +0000

The purpose of this study was to determine differences in bone mineral density (BMD) among adolescent female tennis players (TPs) and nontennis players (NTPs) and to assess body composition as a predictor variable of BMD. Nineteen female TPs and 19 female NTPs, ages 14 to 18 years, participated in this study. Lumbar spine, total hip, femoral neck, forearms BMD, and body composition were assessed using dual-energy X-ray absorptiometry (DXA). Lumbar spine and total hip BMD measurements for TP were greater than NTP. However, these differences were not statistically significant (𝑃=0.37 and 0.12, resp.). TP had significantly greater femoral neck BMD than NTPs (𝑃=0.02). This difference might play an important role in preventing osteoporosis and decreasing the risk of fractures at the hip later in life.

Inhibition of Bone Loss by Cissus quadrangularis in Mice: A Preliminary Report

Thu, 21 Jun 2012 13:57:45 +0000

Women drastically loose bone during and after menopause leading to osteoporosis, a disease characterized by low bone mass increasing the risk of fractures with minor trauma. Existing therapies mainly reduce bone resorption, however, all existing drugs have severe side effects. Recently, the focus is to identify alternative medicines that can prevent and treat osteoporosis with minimal or no side effects. We used Cissus quadrangularis (CQ), a medicinal herb, to determine its effects on bone loss after ovariectomy in C57BL/6 mice. Two-month old mice were either sham operated or ovariectomized and fed CQ diet. After eleven weeks, mice were sacrificed and the long bones scanned using pQCT and μCT. In the distal femoral metaphysis, femoral diaphysis, and proximal tibia, control mice had decreased cancellous and cortical bone, while CQ-fed mice showed no significant differences in the trabecular number, thickness, and connectivity density, between Sham and OVX mice, except for cortical bone mineral content in the proximal tibia. There were no changes in the bone at the tibio-fibular junction between groups. We conclude that CQ effectively inhibited bone loss in the cancellous and cortical bones of femur and proximal tibia in these mice.

Surgical Approach and Laser Applications in BRONJ Osteoporotic and Cancer Patients

Tue, 08 May 2012 13:33:08 +0000

Bisphosphonates-related Osteonecrosis of the Jaw (BRONJ) has been reported with increasing frequency in literature over last years, but its therapy is still a dilemma. One hundred ninety patients affected by BRONJ were observed between January 2004 and November 2011 and 166 treated sites were subdivided in five groups on the basis of the therapeutical approach (medical or surgical, traditional or laser-assisted approach, with or without Low Level Laser Therapy (LLLT)). Clinical success has been defined for each treatment performed as clinical improvement or complete mucosal healing. Combination of antibiotic therapy, conservative surgery performed with Er:YAG laser and LLLT applications showed best results for cancer and noncancer patients. Nonsurgical approach performed on 69 sites induced an improvement in 35 sites (50.7%) and the complete healing in 19 sites (27.5%), while surgical approach on 97 sites induced an improvement in 84 sites (86.6%) and the complete healing in 78 sites (80.41%). Improvement and healing were recorded in 31 (81.5%) and 27 (71.5%) out of the 38 BRONJ sites treated in noncancer patients and in 88 (68.75%) and in 69 (53.9%) out of the 128 in cancer patients.

Osteoporosis in Men

Pawel Szulc, Jean Marc Kaufman, and Eric S. Orwoll — Thu, 12 Apr 2012 16:15:15 +0000

PTH Assays: Understanding What We Have and Forecasting What We Will Have

Jose Gilberto H. Vieira — Tue, 03 Apr 2012 10:30:41 +0000

Parathyroid hormone (PTH) assays have evolved continuously for the last 50 years. Since the first radioimmunoassay was described in 1963, several assays based on immunological identification have been published (first generation assays). The routine assays used nowadays are immunometric “sandwich-type”. They are based on two different monoclonal antibodies, one amino-terminal and the other carboxyl terminal specific. These second generation assays are widely available and adapted to most of the automation platforms. The specificity of the amino terminal antibody defines if the immunometric assay measures only the bioactive PTH circulating form (including the first amino terminal amino acids) or the “intact” PTH, which includes, besides bioactive PTH, other “long” carboxyl-terminal forms, for example, 7–84-PTH. Assays for “intact” PTH are the most commonly available and the potential advantage of the bioactive PTH assays is still debatable. Next generation of assays will be based on different principles, mainly mass spectrometry in samples submitted to a prior purification and fragmentation steps. These assays will provide information about the whole spectra of PTH peptides in circulation, with a significant increase of the information regarding this biologically important peptide hormone.

Genetic Influence of Candidate Osteoporosis Genes in Saudi Arabian Population: A Pilot Study

Mir Sadat-Ali and Haifa A. Al-Turki — Sun, 01 Apr 2012 15:48:32 +0000

Background and Objectives. The purpose of the present study is to find the genes and SNP that influence BMD and postmenopausal Saudi women. Material and Methods. Two-hundred ethnic Saudi Arabian women with a diagnosis of postmenopausal osteoporosis were the subjects of this study. Baseline blood hematology, biochemistry, and bone panel were done. Blood was collected, and three TaqMan-MGB probes were used to analyze SNP variants in ALOX15 (rs7220870), LRP5 (C 25752205 10), and TNFRSF11B (C 11869235 10). Results. The variant of ALOX15 17p13 showed that the BMD of the spine was lower in the AA allele (𝑃 value <0.002) and fractures were highest at 50% compared to CC allele. In the TNFRSF11B gene, BMD of the hip and spine was significantly higher in the GG allele and the history of fractures was significantly higher in GG group. With regard to the LRP5 (C 25752205 10) gene, there was no significant difference between allele groups. Conclusion(s). This study shows that the genetic influence of osteoporosis in the Caucasian and Saudi Arabians population is similar. We believe that the same genetic markers that influence osteoporosis in the Caucasian race could be used for further studies in the Saudi Arabian population.

Normocalcemic versus Hypercalcemic Primary Hyperparathyroidism: More Stone than Bone?

L. M. Amaral, D. C. Queiroz, T. F. Marques, M. Mendes, and F. Bandeira — Sun, 25 Mar 2012 11:01:17 +0000

Introduction. Normocalcemic primary hyperparathyroidism (NPHPT) is considered a variant of the more frequent form of the disease characterized by normal serum calcium levels with high PTH. The higher prevalence of renal stones in patients with HPTP and the well established association with bone disorders show the importance of studies on how to manage asymptomatic patients. Objective. To compare the clinical and laboratory data between the normocalcemic and mild hypercalcemic forms of PHPT. Methods. We retrospectively evaluated 70 patients with PHPT, 33 normocalcemic and 37 mild hypercalcemic. Results. The frequency of nephrolithiasis was 18.2% in normocalcemic patients and 18.9% in the hypercalcemic ones (𝑃=0.937). Fifteen percent of normocalcemic patients had a previous history of fractures compared to 10.8% of hypercalcemic patients, although there was no statistically significant difference (𝑃=0.726). Conclusion. Our data confirms a high prevalence of urolithiasis in normocalcemic primary hyperparathyroidism, but with the preservation of cortical bone. This finding supports the hypothesis that this disease is not an idle condition and needs treatment.