Characteristics Associated with Acute-Phase Response following First Zoledronic Acid Infusion in Brazilian Population with Osteoporosis

We aimed to evaluate characteristics associated with acute-phase response (APR) following first zoledronic acid infusion in a Brazilian cohort. This retrospective cohort study enrolled all adults with osteoporosis who underwent a first zoledronic acid infusion at our centre between June 2015 and June 2019. Clinical demographics (age, sex, diabetes, smoking, body mass index, and previous oral bisphosphonate use) and laboratory data (calcium, parathyroid hormone, renal function, and serum 25-hydroxyvitamin D and carboxy-terminal crosslinked telopeptide of type 1 collagen [CTX], both before and after infusion) were compared between patients with and without APR. We evaluated association magnitude between the presence of APR and clinical variables through logistic regression. This study enrolled 400 patients (women, 80%). APR was observed in 24.5% (n = 98) of patients. The mean symptom duration in days was 3.5 ± 2.8. Patients with APR were younger (67 ± 12 vs. 71 ± 11 years; p = 0.001 ), used oral bisphosphonates less frequently (34% × 50%; p = 0.005 ), and had greater baseline CTX (0.535 ng/mL [0.375, 0.697] × 0.430 [0.249, 0.681]; p = 0.03 ) and ΔCTX (−69 [−76; −50] × −54 [−72; −23]; p = 0.002 ) than those without APR. The other variables were similar between the groups. Only ΔCTX was associated (OR, 0.62; 95% CI 0.41–0.98) with APR after accounting for age and bisphosphonate use. APR occurred in 24.5% of the cohort. Younger age and absence of prior oral bisphosphonate use were associated with APR following first zoledronic acid infusion. APR was associated with ΔCTX (but no other variables) after adjusting for these factors.

Site-Specific Volumetric Skeletal Changes in Women with a Distal Forearm Fracture

Purpose. To assess site-specific volumetric bone and muscle changes, as well as demographic and biochemical changes, in postmenopausal women with a low-energy distal forearm fracture. Methods. In a cross-sectional case-control study, postmenopausal women with a distal forearm fracture were compared with age- and gender-matched controls. In total, 203 postmenopausal women (104 cases and 99 controls), with a mean age of 65 years, were included. Measurements included peripheral quantitative computed tomography (pQCT) and dual-energy X-ray absorptiometry (DXA) as well as blood sampling and questionnaires. Results. Forearm trabecular volumetric BMD and total BMD assessed with pQCT were significantly lower in fracture cases compared to controls ( p < 0.001 ). Significantly higher cross-sectional area, lower cortical BMD, and lower cortical thickness were seen in women with fracture ( p < 0.033 , p < 0.001 , and p < 0.001 , respectively). Postmenopausal women with fracture had significantly lower hip and spine areal BMD assessed with DXA ( p < 0.001 ). Activity level was higher and a history of falling was more frequent in women with fracture ( p < 0.019 and p < 0.001 , respectively). Vertebral fracture was observed in 24 women (22%) with a distal forearm fracture. Muscle area, muscle density, PTH, and 25OHD did not differ between fracture cases and controls. Conclusion. A distal forearm fracture was associated with site-specific and central bone changes. Postmenopausal women with fracture had a larger bone area in combination with a thinner cortex and lower site-specific total BMD. In addition, women with fracture had a higher activity level, an increased occurrence of previous fall accidents, and a high prevalence of vertebral fractures. Forearm muscle composition, PTH, and 25OHD were not associated with forearm fracture. Fracture preventive measures following a low-energy distal forearm fracture seem beneficial.

Association of Postoperative Neutrophil Lymphocyte Ratio (NLR) and Monocyte Lymphocyte Ratio (MLR) with the Presence of Osteoporosis in Japanese Patients after Hip Fracture Surgery: A Retrospective Cohort Study

Background. The diagnosis of osteoporosis is based on bone mineral density measurements expressed as a percentage of the young adult mean (YAM) in Japan. Osteoporosis is defined as YAM <70%, and intervention is recommended at this cutoff. Because osteoporosis has a strong association with systemic metabolic disorders, we postulated that patients with YAM <70% had higher inflammatory biomarker concentrations owing to the higher systemic stress compared with YAM >70%. Method. We retrospectively reviewed 94 patients with low-trauma hip fractures. Blood examinations were performed on postoperative day (POD) 1 and POD 7. We used neutrophil lymphocyte ratio (NLR) and monocyte lymphocyte ratio (MLR) to evaluate postoperative recovery. After dividing the 94 patients into two groups according to a YAM cutoff of 70%, we compared the differences in NLR and MLR. Results. On POD 1, patients with YAM >70% had a median NLR of 5.7 and a median MLR of 0.66, which were significantly lower than for patients with YAM <70% (8.8 and 0.9, respectively). Similarly, on POD 7, patients with YAM >70% had a median NLR of 2.0 and a median MLR of 0.31, which were significantly lower than for patients with YAM <70% (3.5 and 0.43, respectively). Conclusion. A YAM cutoff of 70% is an appropriate intervention threshold regarding postoperative recovery after hip fracture surgery. Mini-Abstract. Patients with YAM >70% showed lower NLR and MLR on POD 1 and POD 7. A YAM cuffoff of 70% is an appropriate intervention threshold regarding postoperative recovery after hip fracture surgery.

FRAX-Based Intervention Thresholds for Osteoporosis Treatment in Ukraine

Objectives. Osteoporosis, in addition to its consequent fracture burden, is a common and costly condition. FRAX® is a well-established, validated, web-based tool which calculates the 10-year probability of fragility fractures. A FRAX model for Ukraine has been available since 2016 but its output has not yet been translated into intervention thresholds for the treatment of osteoporosis in Ukraine; we aimed to address this unmet need in this analysis. Methods. In a referral population sample of 3790 Ukrainian women, 10-year probabilities of major osteoporotic fracture (MOF) and hip fracture separately were calculated using the Ukrainian FRAX model, with and without femoral neck bone mineral density (BMD). We used a similar approach to that first proposed by the UK National Osteoporosis Guideline Group, whereby treatment is indicated if the probability equals or exceeds that of a woman of the same age with a prior fracture. Results. The MOF intervention threshold in females (the age-specific 10-year fracture probability) increased with age from 5.5% at the age of 40 years to 11% at the age of 75 years where it plateaued and then decreased slightly at age 90 (10%). Lower and upper thresholds were also defined to determine the need for BMD, if not already measured; the approach targets BMD measurements to those at or near the intervention threshold. The proportion of the referral populations eligible for treatment, based on prior fracture or similar or greater probability, ranged from 44% to 69% depending on age. The prevalence of the previous fracture rose with age, as did the proportion eligible for treatment. In contrast, the requirement for BMD testing decreased with age. Conclusions. The present study describes the development and application of FRAX-based assessment guidelines in Ukraine. The thresholds can be used in the presence or absence of access to BMD and optimize the use of BMD where access is restricted.

A Phase IV Study of the Safety and Efficacy of CinnoPar® in Iranian Patients with Osteoporosis

The safety of teriparatide has been studied in various phase III and phase IV trials. However, a postmarketing study of the biosimilar of teriparatide, CinnoPar®, has not been conducted on Iranian patients. This was a phase IV study conducted on osteoporotic patients who received an Iranian teriparatide biosimilar with a dose of 20 μg daily. The primary outcome of this study was to monitor for adverse events (AEs). Effectiveness as the secondary outcome was measured using the EQ-5D quality-of-life questionnaire and back pain Visual Analogue Scale (VAS) score. Among 193 analyzed patients between September 2015 and March 2019, the most common AEs were hypercalcemia (4%), nausea, and pain (3%). No deaths, serious AEs, or other significant AEs occurred in this study. The mean EQ-5D scores decreased after the course of the treatment from 2.3 ± 0.66 at the baseline to 2 ± 0.66. The mean back pain VAS scores also decreased from 4.9 ± 3.6 at baseline to 1.8 ± 2.1 at the end of the study. Both changes were statistically significant ( p < 0.001 ). Consistent with the findings of previous studies and the drug monograph, no new safety concern was observed with this biosimilar teriparatide, and the drug was effective based on the VAS score and EQ-5D in osteoporotic patients.

The Effects of Trends in Osteoporosis Treatment on the Incidence of Fractures

Summary. We analyzed the data about the preferences of medication and incidence of fractures between osteoporosis patients from 2012 to 2016. Our results suggested that the number of patients treated with intravenous and subcutaneous injections increased and the incidence of fracture was lower in intravenous and subcutaneous injections than oral medications. Objective. This study focused on the trends in antiosteoporosis drug preferences and compared the incidence of fractures between patients treated orally and those who were exposed to an awareness campaign and assigned to intravenous/subcutaneous treatment. Methods. Our hospital registry included 1,716 osteoporotic women who were over 65 years of age without preexisting vertebral and nonvertebral fractures over 1 year before this study, with bone mineral density (BMD) < −2.5 standard deviation (SD) and fracture assessment tool (FRAX) score > 20%, who were given 1,337 oral and 379 intravenous/subcutaneous prescriptions to treat their osteoporosis. Self-administered surveys (2012, 2013, 2014, 2015, and 2016) collected data on trends of preferences among nine drugs and fracture prevention using relative risk reduction (RRR). Results. The number of patients taking oral prescriptions decreased gradually from 2012 to 2016, while the number of patients treated with intravenous and subcutaneous injections increased. The incidence of fracture was lower in patients receiving intravenous and subcutaneous injections than in patients taking oral medications. Conclusion. These findings indicate a decrease in oral prescriptions for osteoporosis treatment and that treatment for osteoporosis using intravenous or subcutaneous injections of antiosteoporosis drugs is more effective for preventing fractures.

Ascending Aortic Calcification as a Potential Predictor for Low Bone Mineral Density: A Pilot Study

Background. Identifying the factors related to low bone mineral density (BMD) can have significant implications for preventing hip fractures. The correlation between ascending aortic calcification and BMD has never been reported. Therefore, the purpose of the current study is to confirm the hypothesis that ascending aortic calcification can be used as a predictive factor for low BMD and to find a radiographic sign to show it. Method. Plain film and computed tomography (CT) images of the thorax were obtained from 91 patients with hip fractures. Using the images, the calcification line of the ascending aorta adjacent to the aortic arch was evaluated. A prominent calcification line confirmed by both plain film and CT was classified as +2. A line which was ambiguous on plain film but confirmed by CT was classified as +1. Cases with no calcification were categorized as 0 (control). We compared the classified score with the BMD and calculated the kappa coefficient to measure intraobserver reliabilities for this radiographic finding. Results. Twenty-eight patients showed a +2 line, twenty-four patients showed a +1 line, and thirty-nine patients showed 0 lines. The median BMD of each group was 0.37 for the +2 line, 0.45 for the +1 line, and 0.51 for the 0 line. The BMD for the +2 group was significantly lower than the others. The kappa coefficient was approximately 0.6 ( p < 0.01 ). Conclusion. The imaging finding of calcification of the ascending aorta might be considered as a potential surrogate marker of low BMD. In such subjects, BMD might be ordered for the confirmation of diagnosis of osteoporosis. Mini-Abstract. The Aortic Arch Tail Sign, a calcification line on the ascending aorta, was relevant to low BMD in the current study. BMD can be ordered for the confirmation of diagnosis of osteoporosis in a subject incidentally found to have ascending aorta calcification on X-ray or CT.

Implementation of a Postfracture Care Program in a Private Hospital in Colombia

Purpose. To describe the implementation of a postfracture care program in a private hospital in Colombia, the results achieved after the program’s first year, and the challenges encountered. Methods. A cross-sectional descriptive study of the first year’s outcomes. The program was implemented following best practices described in the “Capture the Fracture” framework. We assessed the management of fractures before the launch of the program. A multidisciplinary group was established to collaborate on the diagnosis and treatment of patients with osteoporotic fractures. A full-time program coordinator was appointed. We analyzed the program’s clinical outcomes and limitations. Results. One-hundred and ninety patients were included in the study, with an average age of 76.7. Hip fracture was the most frequent one (33.6%). After the first year of implementing the program, 39.4% of patients received osteoporosis treatment, with an adherence rate of 73%. The incidence of subsequent falls was 5.8% and 1% for new fractures. Conclusions. The implementation of a program for patients’ care with fragility fractures is challenging for healthcare institutions. The role of a full-time coordinator is critical for the proper operation of such programs.

Vitamin D, Calcium, Parathyroid Hormone, and Sex Steroids in Bone Health and Effects of Aging

Bone health of the elderly is a major global health concern, since about 1 in 3 women and 1 in 5 men suffer from bone loss and fractures, often called osteoporosis, in old age. Bone health is a complex issue affected by multiple hormones and minerals. Among all the hormones involved in bone health, calcitriol (also vitamin D), parathyroid, and sex hormones (especially estrogen) have been discussed in this review paper. We have discussed the metabolism of these hormones and their effects on bone health. Vitamin D can be obtained from diet or formed from 7-dehydrocholesterol found under the skin in the presence of sunlight. The active form, calcitriol, causes dimerization of vitamin D receptor and acts on the bones, intestine, and kidney to regulate the level of calcium in blood. Similarly, parathyroid hormone is secreted when the serum level of calcium is low. It helps regulate the level of blood calcium through calcitriol. Sex hormones regulate bone modeling at an early age and remodeling later in life. Loss of ovarian function and a decrement in the level of production of estrogen are marked by bone loss in elderly women. In the elderly, various changes in the calcium and vitamin D metabolism, such as decrease in the production of vitamin D, decrease in dietary vitamin D, decreased renal production, increased production of excretory products, decrease in the level of VDR, and decreased calcium absorption by the intestines, can lead to bone loss. When the elderly are diagnosed with osteoporosis, medications that directly target bone such as bisphosphonates, RANK ligand inhibitors, estrogen and estrogen analogues, estrogen receptor modulators, and parathyroid hormone receptor agonists are used. Additionally, calcium and vitamin D supplements are prescribed.

Muscle-Bone Interactions in Chinese Men and Women Aged 18–35 Years

To characterize bone mineral density (BMD), bone strength, muscle and fat mass, and muscle strength and power in Chinese women (n = 25) and men (n = 28) classified as in the bone accrual phase (18–25 years) or in the peak bone mass phase (26–35 years). Calcium intakes, physical activity levels, and serum vitamin D were measured. Dual-energy X-ray absorptiometry (DXA) assessed body composition, lumbar spine, and hip areal BMD (aBMD) variables and peripheral quantitative computed tomography (pQCT) assessed cortical and trabecular volumetric BMD (vBMD) and bone strength. Muscle strength and power were assessed by grip strength, leg press, and vertical jump tests. Calcium, serum vitamin D, and physical activity levels were similar across age and sex groups. Significant sex differences p<0.05 were found for most body composition variables, hip aBMD, tibia variables, and muscle strength and power. Adjusting for height and weight eliminated most of the significant sex differences. Women showed stronger positive correlations between body composition and bone variables (r = 0.44 to 0.78) than men. Also, correlations between muscle strength/power were stronger in women vs. men (r = 0.43 to 0.82). Bone traits were better related to body composition and muscle function in Chinese women compared to Chinese men aged 18 to 35 years, and peak bone mass seems to be achieved by 25 years of age in both Chinese men and women since there were no differences between the two age groups.