Osteoporotic Therapy Research Articles

Undiagnosed vertebral fragility fractures in patients with distal radius fragility fractures: an opportunity for prevention of morbimortality in osteoporotic patients in developing countries.

This study's main goal was to look into the frequency, location, kind, and severity of asymptomatic vertebral fragility fractures (VFF) in people who had fractures of the fragility of the distal radius. Although VFF is frequently misdiagnosed, it is linked to higher mortality, morbidity, and hip fracture risk. The study also attempted to investigate the relationship between VFF and certain demographic and lifestyle factors, as well as FRAX data, in this patient population. Between January, 2021, and January, 2022, individuals with low-energy distal radial fractures who presented to the emergency room of tertiary care hospital of Karachi, Pakistan, were the subject of a cross-sectional study and were 45years of age or older except those who fitted the exclusion criteria (n = 208). The thoracic and/or lumbar spine was imaged using radiology, and information on demographics, way of life, and FRAX (Fracture Risk Assessment Tool) was gathered. Using the Genant semiquantitative approach, an impartial and blinded orthopaedist identified VF in the images and determined their severity. SPSS version 20 was used to analyse the data. Two hundred eleven (41.21%) of them were found to have radiographic VFF and only 12 (2.34%) of the 512 patients who were tested were getting osteoporotic therapy. The thoracic spine (32.7%), followed by the lumbar spine (43.12%), was the area most frequently afflicted. In 24.17% of the patients, multiple fractures of the thoracolumbar spine were found. The wedge form (54.5%), followed by biconcave (30.81%) and crush (14.7%), was the most prevalent VFF type. The majority of detected VFF were rated as having a 25-40% height loss (64.9%) then severe (> 40%) fractures (35.1%), according to the Genant grading method. Notably, there were no variations in smoking, drinking, BMI, or FRAX score between patients with and without VFF that were statistically significant. Based on our study's findings, it is clear that osteoporotic vertebral fragility fractures occur in almost half of individuals with distal radius fractures. The lumbar spine is notably the most affected region, predominantly with wedge fractures. Given the high prevalence of asymptomatic vertebral fragility fractures (VFF), proactive measures are necessary to mitigate associated risks. Prioritising comprehensive fall risk assessments for these patients and interventions to enhance bone mineral density and strength are crucial. Early identification of asymptomatic VFF enables timely intervention, optimising patient care and minimising the risk of complications in this vulnerable population.

Phytosterols Protect against Osteoporosis by Regulating Gut Microbiota.

Osteoporosis is increasingly prevalent worldwide, representing a major health burden. However, there is a lack of nutritional strategies for osteoporotic therapy. Phytosterols, as natural bioactive compounds, have the potential to alleviate osteoporosis. In this study, a glucocorticoid-induced osteoporosis mouse model and treatment with low and high concentrations of phytosterols for 4 weeks were established. The results demonstrated that compared to the control group, low-concentration phytosterols (LP) (0.3 mg/mL) increased bone mass, improved trabecular microstructure, reduced serum levels of cross-linked C-telopeptide of type I collagen (CTX-1), and elevated serum levels of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3). Conversely, high-concentration phytosterols (0.5 mg/mL) showed no effect. Additionally, we validated the effect of LP in ameliorating osteoporosis using an ovariectomized (OVX)-induced osteoporosis mouse model. Mechanistically, phytosterols altered the microbial composition to counteract glucocorticoid-induced gut microbiota disorder and improve the length and morphology of the small intestine. Particularly, based on selection strategy and correlation analysis, phytosterols increased the relative abundance of Ruminococcus and decreased the relative abundance of Bilophila, which were significantly associated with glucocorticoid-induced osteoporosis indications. Overall, these findings suggest that phytosterols regulate gut microbiota to increase bone mass, thereby exerting an antiosteoporotic effect.

Role of determining trabecular bone score for appointment of osteoporotic therapy (clinical case)

Numerous studies have shown that the trabecular bone score (TBS) in patients with rheumatic diseases and especially in persons receiving glucocorticoids predicts fractures better than the bone mineral density (BMD) of the spine or the value of a 10-year probability of osteoporotic fracture according to the FRAX calculator. This article describes the role of TBS in determining the indications for prescribing anti-osteoporotic treatment on the example of a clinical case of a postmenopausal woman with a confirmed diagnosis of rheumatoid arthritis and a slight decrease in BMD.

Litsea glutinosa extract promotes fracture healing and prevents bone loss via BMP2/SMAD1 signaling.

Estrogen deficiency is one of the main causes for postmenopausal osteoporosis. Current osteoporotic therapies are of high cost and associated with serious side effects. So there is an urgent need for cost-effective anti-osteoporotic agents. Anti-osteoporotic activity of Litsea glutinosa extract (LGE) is less explored. Moreover, its role in fracture healing and mechanism of action is still unknown. In the present study we explore the osteoprotective potential of LGE in osteoblast cells and fractured and ovariectomized (Ovx) mice models. Alkaline phosphatase (ALP), MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and mineralization assays revealed that LGE treatment increased osteoblast cell differentiation, viability and mineralization. LGE treatment at 0.01 μg increased the expression of BMP2, PSMAD, RUNX2 and type 1 col. LGE also mitigated RANKL-induced osteoclastogenesis. Next, drill hole injury Balb/C mice model was treated with LGE for 12 days. Micro-CT analysis and Calcein labeling at the fracture site showed that LGE (20 mg/kg) enhanced new bone formation and bone regeneration, also increased expression of BMP2/SMAD1 signaling genes at fracture site. Ovx mice were treated with LGE for 1 month. μCT analysis indicated that the treatment of LGE at 20 mg/kg dose prevented the alteration in bone microarchitecture and maintained bone mineral density and bone mineral content. Treatment also increased bone strength and restored the bone turnover markers. Furthermore, in bone samples, LGE increased osteogenesis by enhancing the expression of BMP2/SMAD1 signaling components and decreased osteoclast number and surface. We conclude that LGE promotes osteogenesis via modulating the BMP2/SMAD1 signaling pathway. The study advocates the therapeutic potential of LGE in osteoporosis treatment.

LBSAT140 Mortality Risk Following Atypical Femoral Fracture: A Systematic Review And Meta-analysis

Abstract Introduction Proximal femoral fracture in elderly (>60 years of age) is known to be associated with a high one-year mortality risk of 21.2% (1). Studies have shown that the mortality rate of atypical femoral fracture (AFF) may be lower than that of typical proximal femoral fracture (2), although results from existing studies are inconsistent. Therefore, we aimed to summarize all available data, using systematic review and meta-analysis, to estimate the one-year mortality risk following AFF and risk ratio of mortality following AFF versus typical femoral fracture (TFF). Methods Potentially eligible studies were identified from Medline and EMBASE databases from inception to February 2022 using a search strategy that comprised keywords "Atypical Femoral Fracture" and "Mortality". Any eligible study must consist of a cohort of patients with AFF. Then, the study must report a one-year mortality risk following AFF or effect estimates with 95% confidence intervals (95% CIs) comparing mortality risks between patients with AFF and TFF. Data were retrieved from each study and were combined using the generic inverse variance method. Results A total of 8,967 articles were identified. After two rounds of independent review by three investigators, we identified 7 studies reporting one-year mortality risks of AFF and 3 studies comparing mortality risks of AFF versus TFF. These studies were included into the meta-analysis. The pooled one-year mortality risk following atypical femoral fracture of 0.10 (95% CI, 0. 05 - 0.16; with high heterogeneity, I2 93.3%). The funnel plot was asymmetric in favor of studies that reported high one-year mortality risks. In the meta-analysis comparing the mortality risks following AFF versus TFF, no significant difference in mortality risks was found between the two conditions, with the pooled risk ratio of 0.98 (95% CI 0.78 - 1.25; with high heterogeneity, I2 96.8%). Conclusion This systematic review and meta-analysis revealed that the one-year mortality risk following AFF was approximately 10%, which may be lower than the reported mortality risk after typical hip fracture of around 20% (1). However, no significant difference was found in the meta-analysis of studies that compared the mortality risks of the two conditions, suggesting the | need for further investigation. The results will be useful for risk-benefit discussions on initiation of antiresorptive and anabolic osteoporotic therapy.

Objectively Measured Physical Activity, Sedentary Behavior, and Incident Fracture in Older Women: The OPACH Study

Women aged 65 and older experience nearly three-fourths of the 2 million osteoporotic fractures annually in the US, yet whether accelerometer-measured volumes and intensities of physical activity and sedentary behavior (SB) are associated with reduced fracture risk is understudied. We investigated associations of accelerometer-measured light physical activity (LPA), moderate-to-vigorous physical activity (MVPA), sedentary time (ST), and mean sedentary bout duration (MBD) with incident clinical fractures (hip, vertebral, pelvis, lower leg, upper arm, forearm, and wrist) in the WHI OPACH cohort. Participants (N=6248; mean±SD age=78.6±6.7; 34% Black, 17% Hispanic) without prior hip fracture wore the ActiGraph GT3X+ for 7 days between May 2012-April 2014 and were followed through March 2020 for incident clinical fracture (N=711). Cox models estimated hazard ratios (HR) and 95% confidence intervals (CI), adjusting for age, race-ethnicity, education, alcohol, smoking, height, weight, falls history, RAND-36 physical function, diabetes, thiazide use, prescription osteoporotic therapy, and age at menopause. The HR(95% CI) across MVPA quartiles was 1.00(reference), 1.15(0.93-1.41), 0.90(0.72-1.13), and 0.79(0.61-1.02); p-trend=0.01. The HR(95% CI) for a one-interquartile range increment in MVPA (42 minutes/day) was 0.86(0.76-0.97). Associations were modified by prescription osteoporotic therapy [no: HR=0.77(0.66-0.89), yes: HR=1.03(0.85-1.25); p-interaction=0.01] and varied in magnitude by age[<80: HR=0.78(0.64-0.96), ≥80: HR=0.92(0.79-1.07); p-interaction=0.09], BMI [<30 kg/m2: HR=0.85(0.75-0.97), ≥30 kg/m2: HR=0.90(0.67-1.19); p-interaction=0.08], and race-ethnicity [Black: HR =0.63(0.44-0.89), Hispanic: HR =0.78(0.56-1.09), White: HR =0.92(0.80-1.06); p-interaction=0.16]. LPA, ST, or MBD were not associated with incident fractures. These data suggest that MVPA may reduce and not increase fracture risk and that LPA and SB do not increase fracture risk.

The effects of alendronate on the suppression of bone resorption and the promotion of cartilage formation in the human mosaicplasty donor site: A randomized, double-blind, placebo-controlled prospective study

BackgroundWe previously reported that early alendronate administration accelerated bone formation and improved the quality of repaired cartilage in the donor site in rabbits. To investigate whether alendronate administration has effects in humans similar to those observed in rabbits. MethodsThe study cohort included 35 patients over the age of 12-years old who underwent mosaicplasty without osteoporotic therapy from March 2011 to October 2012. The donor sites were medial or lateral in the patellofemoral joint. Placebo (P) or Bonalon containing 35 mg of alendronate (A) was administered orally every week for 8 weeks. The cohort comprised 15 male and 20 female, including 14 right and 21 left knees. The mean age at the time of surgery was 57.1 years. Bone formation was examined using computer tomography and lateral knee radiography, and cartilage formation was examined using magnetic resonance imaging (MRI), second-look assessment, and intraoperative acoustic evaluation. The clinical outcomes were assessed using the Japanese Orthopaedic Association knee score and visual analog scale (VAS). Bone and cartilage formation in the donor site and clinical outcomes were assessed at 3, 6, and 12 months after mosaicplasty. ResultsThe ratio of TRAP-5b in group A was significantly smaller than that in group P at 2 and 8 weeks after mosaicplasty. The extent of bone formation in the donor sites in group A was significantly greater than that in group P at 3 and 6 months after mosaicplasty. Cartilage formation did not differ significantly between the two groups as determined by MRI, macroscopic assessment, and intraoperative acoustic evaluation. Clinical outcomes did not differ significantly between the two groups, and no negative clinical outcomes were observed. ConclusionEarly alendronate administration accelerated bone formation but not cartilage formation in the mosaicplasty donor site in humans.

Denosumab-induced hypocalcemia in patients with osteoporosis: can you know who will get low?

RCTs have reported a 0.05-1.7% rate of hypocalcemia in denosumab-treated postmenopausal women with osteoporosis, but long-term real-life data are lacking. We assessed the rate of hypocalcemia in osteoporotic community-dwelling patients treated with denosumab. A retrospective analysis was conducted based on medical records (2010-2018) from a large HMO. An albumin-adjusted serum calcium concentration lower than 8.5mg/dL was defined as hypocalcemia. We included 2005 patients (93% women, mean age 76 ± 9years). Hypocalcemia developed during treatment in 149 patients (7.4%; 1% less than 8mg/dL): in 66 after 0.5-1years; 48 after 1-2years; 35 after > 2years. On comparison of the hypocalcemic and normocalcemic patients, the strongest predictors of hypocalcemia were pretreatment levels of albumin-adjusted serum calcium (9.1 ± 0.4 vs. 9.4 ± 0.5mg/dL, respectively; p < 0.05) and creatinine (0.9 ± 0.5 vs. 0.8 ± 0.3mg/dL, respectively; p < 0.05). The hypocalcemia rate increased in parallel to a decrease in eGFR (p = 0.032 for the difference between eGFR ranges). Baseline calcium level ≤ 9.31mg/dL predicted hypocalcemia with a sensitivity of 77% and specificity of 56%. A model of (- 2)*calcium + creatinine predicted hypocalcemia (3.7% when lower and 17.1% when higher than - 17.4). Gender, age, 25-hydroxyvitamin-D, parathyroid hormone, alkaline phosphatase, and whether denosumab was given as first or advanced line of osteoporotic therapy had no predictive value. Real-life rates of denosumab-induced hypocalcemia are higher than previously reported. Hypocalcemia might develop after each dose of denosumab in ongoing treatment. Adequate calcium and vitamin D supplementation are needed. Serum calcium monitoring is advised in high-risk patients for early detection of severe hypocalcemia.

Bisphosphonates Influence and Pain Assessment in Mobilization of Patients with Fragility Fracture of the Pelvis

Fragility fractures of the pelvis have lately gained interest due to the increased incidence caused by aging populations. The aim of the study was to evaluate the results of the therapy in patients with pelvic fragility fracture admitted between January 2015 and September 2018 St. Spiridon Emergency Hospital in Iasi in order to improve the therapeutic approach. We assessed the correlation between pain and the early mobilization under the weight bearing condition in patients with and without osteoporotic therapy in history. The study emphasizes the role of pain in recovery process and underline the serious consequences of the late detection of bone fragility. Our study had revealed that previous osteoporotic treatment has benefits in the event of a fracture. As a result of this analysis, we consider that the age for the prophylactic measures in bone fragility should go below 60 years.

Bone Turnover Status: Classification Model and Clinical Implications.

Aim: To develop a practical model for classification bone turnover status and evaluate its clinical usefulness.Methods: Our classification of bone turnover status is based on internationally recommended biomarkers of both bone formation (N-terminal propeptide of type1 procollagen, P1NP) and bone resorption (beta C-terminal cross-linked telopeptide of type I collagen, bCTX), using the cutoffs proposed as therapeutic targets. The relationships between turnover subtypes and clinical characteristic were assessed in1223 hospitalised orthogeriatric patients (846 women, 377 men; mean age 78.1±9.50 years): 451(36.9%) subjects with hip fracture (HF), 396(32.4%) with other non-vertebral (non-HF) fractures (HF) and 376 (30.7%) patients without fractures.Resalts: Six subtypes of bone turnover status were identified: 1 - normal turnover (P1NP>32 μg/L, bCTX≤0.250 μg/L and P1NP/bCTX>100.0[(median value]); 2- low bone formation (P1NP ≤32 μg/L), normal bone resorption (bCTX≤0.250 μg/L) and P1NP/bCTX>100.0 (subtype2A) or P1NP/bCTX<100.0 (subtype 2B); 3- low bone formation, high bone resorption (bCTX>0.250 μg/L) and P1NP/bCTX<100.0; 4- high bone turnover (both markers elevated ) and P1NP/bCTX>100.0 (subtype 4A) or P1NP/bCTX<100.0 (subtype 4B). Compared to subtypes 1 and 2A, subtype 2B was strongly associated with nonvertebral fractures (odds ratio [OR] 2.0), especially HF (OR 3.2), age>75 years and hyperparathyroidism. Hypoalbuminaemia and not using osteoporotic therapy were two independent indicators common for subtypes 3, 4A and 4B; these three subtypes were associated with in-hospital mortality. Subtype 3 was associated with fractures (OR 1.7, for HF OR 2.4), age>75 years, chronic heart failure (CHF), anaemia, and history of malignancy, and predicted post-operative myocardial injury, high inflammatory response and length of hospital stay (LOS) above10 days. Subtype 4A was associated with chronic kidney disease (CKD), anaemia, history of malignancy and walking aids use and predicted LOS>20 days, but was not discriminative for fractures. Subtype 4B was associated with fractures (OR 2.1, for HF OR 2.5), age>75 years, CKD and indicated risks of myocardial injury, high inflammatory response and LOS>10 days.Conclusions: We proposed a classification model of bone turnover status and demonstrated that in orthogeriatric patients altered subtypes are closely related to presence of nonvertebral fractures, comorbidities and poorer in-hospital outcomes. However, further research is needed to establish optimal cut points of various biomarkers and improve the classification model.

Functional block of IL-17 cytokine promotes bone healing by augmenting FOXO1 and ATF4 activity in cortical bone defect model.

The immune system plays important role in the fracture healing process. However, fracture healing is prolonged in disorders associated with systemic inflammation. Fracture healing is decelerated in osteoporosis, condition linked with systemic inflammation. Bone regeneration therapies like recombinant human BMP2 are associated with serious side effects. Studies have been carried out where agents like denosumab and infliximab enhance bone regeneration in osteoporotic conditions. Our previous studies show the osteoprotective and immunoprotective effects of neutralizing IL-17 antibody. Here, we determine the effect of IL-17 neutralizing antibody on new bone regeneration and compare its efficacy with known osteoporotic therapies. For the study, female BALB/c mice were ovariectomized or sham operated and left for a month followed by a 0.6-mm drill-hole injury in femur mid-diaphysis. The treatment was commenced next day onwards with anti-IL-17, anti-RANKL (Receptor activator of nuclear factor kappa-B ligand), parathyroid hormone (PTH), or alendronate for a period of 3, 10, or 21days. Animals were then autopsied, and femur bones were dissected out for micro-CT scanning, confocal microscopy, and gene and protein expression studies. Micro-CT analysis showed that anti-IL-17 antibody promoted bone healing at days 10 and 21, and the healing effect observed was significantly better than Ovx, anti-RANKL antibody, and ALN, and equal to PTH. Anti-IL-17 also enhanced new bone regeneration as assessed by calcein-labeling studies. Additionally, anti-IL-17 therapy enhanced expression of osteogenic markers and decreased oxidative stress at the injury site. Overall, our study demonstrates bone healing and regeneration potential of neutralizing IL-17 antibody in osteoporotic fractures.

Recipient Glycemic Micro-environments Govern Therapeutic Effects of Mesenchymal Stem Cell Infusion on Osteopenia.

Therapeutic effects of mesenchymal stem cell (MSC) infusion have been revealed in various human disorders, but impacts of diseased micro-environments are only beginning to be noticed. Donor diabetic hyperglycemia is reported to impair therapeutic efficacy of stem cells. However, whether recipient diabetic condition also affects MSC-mediated therapy is unknown. We and others have previously shown that MSC infusion could cure osteopenia, particularly in ovariectomized (OVX) mice. Here, we discovered impaired MSC therapeutic effects on osteopenia in recipient type 1 diabetes (T1D). Through intensive glycemic control by daily insulin treatments, therapeutic effects of MSCs on osteopenia were maintained. Interestingly, by only transiently restoration of recipient euglycemia using single insulin injection, MSC infusion could also rescue T1D-induced osteopenia. Conversely, under recipient hyperglycemia induced by glucose injection in OVX mice, MSC-mediated therapeutic effects on osteopenia were diminished. Mechanistically, recipient hyperglycemic micro-environments reduce anti-inflammatory capacity of MSCs in osteoporotic therapy through suppressing MSC interaction with T cells via the Adenosine monophosphate-activated protein kinase (AMPK) pathway. We further revealed in diabetic micro-environments, double infusion of MSCs ameliorated osteopenia by anti-inflammation, attributed to the first transplanted MSCs which normalized the recipient glucose homeostasis. Collectively, our findings uncover a previously unrecognized role of recipient glycemic conditions controlling MSC-mediated therapy, and unravel that fulfillment of potent therapeutic effects of MSCs requires tight control of recipient micro-environments.

Experimental osteoporosis in sheep--mechanical and histological approach.

The implementation of new methods of osteoporotic therapy requires tests on animal model. The use of sheep as model has numerous advantages over other animals. The aim of this study was to describe the change in parameters in sheep with osteoporosis induced using steroids and ovariorectomy methods as opposed to the parameters in healthy sheep. The study was performed on female "merinos" breed sheep divided into the three groups: negative control (NC)--healthy animals, positive control (PC)--ovariorectomized animals and steroid control group (SC)--in which methylprednisolone was administered. This paper presents histological and ultrastructural examination with mechanical comparative tests for force/strength values as well as indentation tests of joint cartilage. The obtained results confirm the loss of bone mass associated with mineral composition content in bones, which has an influence on bone strength.

Characterising bone material composition and structure in the ovariectomized (OVX) rat model of osteoporosis.

The ovariectomized (OVX) rat model is well established in investigations of osteoporosis and osteoporotic therapies. Advent of techniques such as Fourier-transform infrared (FTIR) spectroscopy and small angle X-ray scattering (SAXS) facilitate characterization of bone composition and mineral structure, respectively, which are key determinants of bone strength. Limited publications exist on the implementation of these techniques in the OVX rat model. At 12 weeks of age, female Sprague-Dawley rats were either sham-operated (n = 6) or ovariectomized (n = 6) and sacrificed 18 weeks later. L2 lumbar vertebrae and proximal tibiae were assessed by µCT, FTIR and SAXS. Presence of extensive trabecular deterioration in the µCT data confirmed the onset of osteoporosis. FTIR compositional parameters were determined including measures of degree of mineralization, crystallinity, collagen maturity and acid phosphate content. Mineral crystal thickness was determined from the SAXS data using two approaches available in literature. Compositionally, a decline in the heterogeneity of acid phosphate content was observed while measures of crystallinity and collagen maturity remained unaltered. Using an iterative curve fitting method, OVX-induced increases in the mineral crystal thickness of 3.8 and 7.8 % (p < 0.05) were noted in the trabecular of the vertebra and tibia, respectively. In conclusion, implementation of FTIR and SAXS techniques in the OVX rat model, identified no significant compositional changes while substantiating thickening of the mineral crystals as a general structural feature of OVX-induced osteoporosis in rats.

THE POSSIBLE INFLUENCE OF BISPHOSPHONATE THERAPY AND ITS COMBINATION WITH STATINS ON PARAMETERS OF AORTIC STIFFNESS IN WOMEN WITH POSTMENOPAUSAL OSTEOPOROSIS

The study shows that addition of statins to osteoporotic therapy in postmenopausal women with different cardiovascular risk beside desired hypolipidemic effect and reduction of arterial stiffness also elevates BMD at femoral neck by 4,9% from the baseline (p&lt;0.05). Bisphosphonates therapy in postmenopausal women gives additional reduction of central systolic arterial pressure of 4.1 mm Hg with the tendency to improvement in the arterial stiffness. The dynamics of aortal stiffness was correlated with changers in intensity of bone remodeling (for N-terminal propeptides of type I procollagen (P1NP) p =0.47, p=0.019; for carboxyl-terminal telopeptide of collagen type I (CITP1) p=0.40, p=0.05) as well as systolic blood pressure (r=0.52, p=0.008). Conclusions. Bisphosphonate therapy and its combination with statins may influence the on parameters of blood pressure and aortic stiffness in women with postmenopausal osteoporosis.

Medication monitoring and optimization: a targeted pharmacist program for effective and cost-effective improvement of chronic therapy adherence.

Community pharmacies provide a promising platform for monitoring and improving therapy adherence and providing pharmaceutical care. Structured methods and appropriate software are important tools to increase pharmacist effectiveness and improve health outcomes. In 2006, the Medication Monitoring and Optimization (MeMO) program was introduced in several community pharmacies in the Netherlands. MeMO facilitates targeted and continuous patient-centered pharmaceutical care around chronic medication, such as for osteoporosis, cardiovascular disease, and asthma/chronic obstructive pulmonary disease (COPD). To describe the MeMO program and summarize findings from publications on its effectiveness, patient satisfaction, and cost-effectiveness. In the first part of this article, the MeMO program is extensively described. In the second part, a review of the evidence of effectiveness, cost-effectiveness, and patient satisfaction of the MeMO program is provided. Evidence is based on 5 previously published articles. The MeMO program starts with structured counseling sessions with patients at the initiation and follow-up of chronic therapies. This process is followed by a continuous phase in which patients' therapy adherence is monitored on a monthly basis, using standardized search algorithms in the pharmacy database. When the algorithm detects a patient's discontinuation of therapy, tailored interventions are used to improve adherence and optimize pharmacotherapy. For osteoporosis patients, treatment discontinuation with bisphosphonates after 1 year dropped from 31.7% to 16.1% (P less than 0.001). This program was shown to be cost-effective in patients initiating osteoporotic therapy. Future scenarios with lower drug prices (e.g., from generic prescribing) result in cost savings for the MeMO program. For lipid-lowering drugs, the MeMO program has been shown to lower therapy discontinuation after 1 year from 25.9% to 13.6% (P less than 0.001). By extrapolating these results to patients' lifetimes, the intervention was estimated to be cost-effective, with gains for primary prevention of cardiovascular events, and even cost saving in secondary prevention. Results from the ongoing MeMO asthma/COPD program are promising, showing marked improvements in therapy control and quality of life for asthma and COPD patients. Almost all patients participating in MeMO programs are satisfied with the pharmacy team and have gained knowledge of the effectiveness and administration of their medications and the importance of therapy adherence. The MeMO program is an effective and structured method to improve patients' adherence to chronic medication in the field of osteoporosis, lipid-lowering drugs, and asthma/COPD and is well received by patients. By targeting the program toward nonadherent and high-risk patients, the program showed favorable cost-effectiveness.

Melatonin effects on bone: potential use for the prevention and treatment for osteopenia, osteoporosis, and periodontal disease and for use in bone‐grafting procedures

An important role for melatonin in bone formation and restructuring has emerged, and studies demonstrate the multiple mechanisms for these beneficial actions. Statistical analysis shows that even with existing osteoporotic therapies, bone-related disease, and mortality are on the rise, creating a huge financial burden for societies worldwide. These findings suggest that novel alternatives need to be developed to either prevent or reverse bone loss to combat osteoporosis-related fractures. The focus of this review describes melatonin's role in bone physiology and discusses how disruption of melatonin rhythms by light exposure at night, shift work, and disease can adversely impact on bone. The signal transduction mechanisms underlying osteoblast and osteoclast differentiation and coupling with one another are discussed with a focus on how melatonin, through the regulation of RANKL and osteoprotegerin synthesis and release from osteoblasts, can induce osteoblastogenesis while inhibiting osteoclastogenesis. Also, melatonin's free-radical scavenging and antioxidant properties of this indoleamine are discussed as yet an additional mechanism by which melatonin can maintain one's bone health, especially oral health. The clinical use for melatonin in bone-grafting procedures, in reversing bone loss due to osteopenia and osteoporosis, and in managing periodontal disease is discussed.

Influence of education, marital status, occupation, and the place of living on skeletal status, fracture prevalence, and the course and effectiveness of osteoporotic therapy in women in the RAC-OST-POL Study

The RAC-OST-POL population-based, epidemiological study provided data concerning the influence of education, marital status, occupation, and the place of living (residence) on skeletal status, fracture prevalence, and the course and effectiveness of osteoporotic therapy in 625 women older than 55 years, all of them recruited from the District of Raciborz in Poland. Their mean age was 66.4 ± 7.8 years. All the women completed a specially designed questionnaire. The skeletal status was assessed by femoral neck (FN) and total hip (TH) densitometry, using a Lunar DPX system (USA). In univariate analyses, taking into consideration the age differences, bone mineralization was dependent on marital status (Z score for FN and TH was significantly higher in widows than in divorcees; p < 0.05), place of residence (better results in rural areas; p < 0.05), and occupation (better in standing than sitting jobs; p < 0.05 for FN Z score and p < 0.01 for TH Z score). The multivariate model allowed us to verify that only place of living and type of occupation had a significant influence on densitometry results. In direct comparison, fracture prevalence seemed to be borderline significantly more common in widows (33.5%) and least common among divorcees (11.8%) (χ(2) = 6.9, df = 3, p = 0.07), but reanalysis performed after age adjustment excluded a true impact of marital status on fracture occurrence. Other factors did not affect fracture occurrence. Some factors influenced the use of medications for osteoporosis: higher level of education was associated with a more frequent use of vitamin D (χ(2) = 8.49, df = 3, p < 0.05) and of hormone replacement therapy (HRT) (χ(2) = 35.7, df = 3, p < 0.00001). HRT was most commonly used by unmarried women (30%) and least commonly by divorcees (11.8%) (χ(2) = 11.7, df = 3, p = 0.01). Vitamin D was more often used among women from the urban area of Raciborz than by those from surrounding rural areas (χ(2) = 9.2, df = 1, p < 0.01). The frequency of use of the three aforementioned medications was associated with the character of occupation. Women with sedentary jobs demonstrated the highest frequency of intake for vitamin D (χ(2) = 9.92, df = 3, p < 0.05) and HRT (χ(2) = 19.48, df = 3, p < 0.001) as well as for other antiresorptive medications (χ(2) = 8.18, df = 3, p < 0.05). We concluded that the results of the epidemiological study demonstrate that both skeletal status and use of antiosteoporotic medications were partially modified by analyzed social factors, whereas fracture prevalence was generally independent from those factors. These data suggest that education, marital status, place of living, and type of occupation may have impacts on implementation of osteoporosis-preventing health programs.

Osteoporosis and diabetes mellitus

Introduction: Diabetes mellitus (DM) and osteoporotic fractures are major causes of mortality and morbidity in older subjects. Recent reports have revealed close association between fracture risk and DM types 1 and 2 (DM1 and DM2, respectively). Aim of this review is to highlight the importance of these diseases in the elderly and examine certain etiopathogenetic aspects of DM associated osteoporosis, which could be useful in management of diabetic patients. Materials and methods: We searched the Embase and PubMed databases using diabetes, osteoporosis, and bone mineral density (BMD) as search terms and 1989-2009 as publication dates. Discussion: The risk of fractures seems to be increased in both types of DM although DM2 seems to be associated with normal-high BMDs compared with the normal population. This apparent paradox could reflect greater bone frailty in diabetic patients that are unrelated to adipose tissue, hyperinsulinemia, deposition of advanced glycosylation end products in collagen, reduced serum IGF-1 levels, hypercalciuria, renal failure, microangiopathy, and/or inflammation. Diabetic patients’ propensity to fall and multiple comorbidities might also explain their higher fracture rates. The effects of drugs that inhibit bone resorption in diabetic patients are probably similar to those obtained in nondiabetics although there is little information on this issue. In general, effective treatment of diabetes has positive effects on bone metabolism. Metformin acts directly on bone tissue, reducing AGE accumulation, and insulin has direct effects on osteoclast activity. In contrast, the thiazolidinediones seem to have negative effects since they orient mesenchymal progenitor cell differentiation toward adipose rather than bone tissue. Incretin therapy is a newer approach that appears to modify interactions between nutrition and bone turnover (e.g., postprandial suppression of bone resorption). Conclusions: Better understanding of how diabetes and its treatment influence bone tissue could lead to more effective strategies for preventing fractures in diabetic patients. More investigation is needed to determine whether conventional osteoporotic therapy is fully effective in patients with DM.

Sesamin stimulates osteoblast differentiation through p38 and ERK1/2 MAPK signaling pathways

BackgroundOsteoporosis is a worldwide health problem predominantly affecting post-menopausal women. Therapies aimed at increasing bone mass in osteoporetic patients lag behind comparable investigation of therapeutic strategies focusing on the bone resorption process. Sesamin, a major lignan compound found in Sesamun indicum Linn., has a variety of pharmacological effects, though its activity on bone cell function is unclear. Herein we examine the effect of this lignan on osteoblast differentiation and function.MethodCell cytotoxicity and proliferative in hFOB1.19 were examined by MTT and alamar blue assay up to 96 h of treatment. Gene expression of COL1, ALP, BMP-2, Runx2, OC, RANKL and OPG were detected after 24 h of sesamin treatment. ALP activity was measured at day 7, 14 and 21 of cultured. For mineralized assay, ADSCs were cultured in the presence of osteogenic media supplement with or without sesamin for 21 days and then stained with Alizarin Red S. MAPK signaling pathway activation was observed by using western blotting.ResultsSesamin promoted the gene expression of COL1, ALP, OCN, BMP-2 and Runx2 in hFOB1.19. On the other hand, sesamin was able to up-regulate OPG and down-regulate RANKL gene expression. ALP activity also significantly increased after sesamin treatment. Interestingly, sesamin induced formation of mineralized nodules in adipose derived stem cells (ADSCs) as observed by Alizarin Red S staining; this implies that sesamin has anabolic effects both on progenitor and committed cell stages of osteoblasts. Western blotting data showed that sesamin activated phosphorylation of p38 and ERK1/2 in hFOB1.19.ConclusionsThe data suggest that sesamin has the ability to trigger osteoblast differentiation by activation of the p38 and ERK MAPK signaling pathway and possibly indirectly regulate osteoclast development via the expression of OPG and RANKL in osteoblasts. Therefore, sesamin may be a promising phytochemical that could be developed for supplementation of osteoporotic therapy.