Bisphosphonates and lower mortality risk: when it sounds to be good to be true …

Bone mineral density gains with a second 12-month course of romosozumab therapy following placebo or denosumab Abstract Summary Romosozumab is a therapy that stimulates bone formation and reduces bone resorption. In this study of postmenopausal women with low BMD, a second course of romosozumab following a period off treatment or on denosumab increased or maintained BMD, respectively, and was well tolerated, providing insight into treatment sequence options. Introduction In patients with high fracture risk, therapies that stimulate bone formation provide rapid BMD gains; currently available agents, parathyroid hormone receptor agonists, are limited to a 2-year lifetime exposure and generally used for a single treatment course. However, for long-term osteoporosis management, a second treatment course may be appropriate. Romosozumab, a therapy with the dual effect of increasing bone formation and decreasing bone resorption, reduces fracture risk within 12 months. Here, we report efficacy and safety of a second romosozumab course. Methods In this phase 2, dose-finding study, postmenopausal women with low bone mass (T-score ≤ − 2.0 and ≥ − 3.5) received romosozumab or placebo (month 0–24) followed by placebo or denosumab (month 24–36); participants then received a year of romosozumab (month 36–48). Results Of 167 participants who entered the month 36–48 period, 35 had been initially randomized to romosozumab 210 mg monthly. In participants who received romosozumab 210 mg monthly followed by placebo, a second romosozumab course (n = 19) increased BMD by amounts similar to their initial treatment (month 0–12) at the lumbar spine (12.4%; 12.0%, respectively) and total hip (6.0%; 5.5%, respectively). Following denosumab, a second romosozumab course (n = 16) increased BMD at the lumbar spine (2.3%) and maintained BMD at the total hip. Safety profiles were similar between first and second romosozumab courses. Conclusions After 12 months off-treatment, a second romosozumab course again led to rapid and large BMD gains. Following denosumab, BMD gains with romosozumab were smaller than with initial treatment. No new safety findings were observed during the second course.

Bisphosphonate drug holidays

Drug holidays in osteoporosis treatment: mind the gaps!

Calcifediol or vitamin D to optimize vitamin D status: Reply to letter of M Sosas

Systematic screening using FRAX ® leads to increased use of, and adherence to, anti-osteoporosis medications: an analysis of the UK SCOOP trial Abstract Summary In the large community-based SCOOP trial, systematic fracture risk screening using FRAX® led to greater use of AOM and greater adherence, in women at high fracture risk, compared with usual care. Introduction In the SCreening of Older wOmen for Prevention of fracture (SCOOP) trial, we investigated the effect of the screening intervention on subsequent long-term self-reported adherence to anti-osteoporosis medications (AOM). Methods SCOOP was a primary care–based UK multicentre trial of screening for fracture risk. A total of 12,483 women (70–85 years) were randomised to either usual NHS care, or assessment using the FRAX® tool ± dual-energy X-ray absorptiometry (DXA), with medication recommended for those found to be at high risk of hip fracture. Self-reported AOM use was obtained by postal questionnaires at 6, 12, 24, 36, 48 and 60 months. Analysis was limited to those who initiated AOM during follow-up. Logistic regression was used to explore baseline determinants of adherence (good ≥ 80%; poor < 80%). Results The mean (SD) age of participants was 75.6 (4.2) years, with 6233 randomised to screening and 6250 to the control group. Of those participants identified at high fracture risk in the screening group, 38.2% of those on treatment at 6 months were still treated at 60 months, whereas the corresponding figure for the control group was 21.6%. Older age was associated with poorer adherence (OR per year increase in age 0.96 [95% CI 0.93, 0.99], p = 0.01), whereas history of parental hip fracture was associated with greater rate adherence (OR 1.67 [95% CI 1.23, 2.26], p < 0.01). Conclusions Systematic fracture risk screening using FRAX® leads to greater use of AOM and greater adherence, in women at high fracture risk, compared with usual care.

Understanding patients’ preferences for osteoporosis treatment: the impact of patients’ characteristics on subgroups and latent classes Abstract Summary This study revealed patterns in osteoporosis patients’ treatment preferences, which cannot be related to socio-demographic or clinical characteristics, implicating unknown underlying reasons. Therefore, to improve quality of care and treatment, patients should have an active role in treatment choice, irrespective of their characteristics. Introduction Patient centeredness is important to improve the quality of care. Accounting for patient preferences is a key element of patient centeredness, and understanding preferences are important for successful and adherent treatment. This study was designed to identify different preferences profiles and to investigate how patient characteristics influence treatment preferences of patients for anti-osteoporosis drugs. Methods Data from a discrete choice experiment among 188 osteoporotic patients were used. The hypothetical treatment options were characterized by three attributes: treatment efficacy, side effects, and mode/frequency of administration. A mixed logit model was used to measure heterogeneity across the sample. Subgroup analyses were conducted to identify potential effect of patient characteristics. Latent class modeling (LCM) was applied. Associations between patients’ characteristics and the identified latent classes were explored with chi-square. Results All treatment options were important for patients’ decision regarding osteoporotic treatment. Significant heterogeneity was observed for most attributes. Subgroup analyses revealed that patients with a previous fracture valued efficacy most, and patients with a fear of needles or aged > 65 years preferred oral tablets. Elderly patients disliked intravenous medication. Three latent classes were identified, in which 6-month subcutaneous injection was preferred in two classes (86%), while oral tablets were preferred in the third class (14%). No statistically significant associations between the profiles regarding socio-demographic or clinical characteristics could be found. Conclusions This study revealed patterns in patients’ preferences for osteoporosis treatment, which cannot be related to specific socio-demographic or clinical characteristics. Therefore, patients should be involved in clinical decision-making to reveal their preferences.

Multiple vertebral compression fractures after sleeve gastrectomy and a subsequent pregnancy: a case report Abstract We report that a 33-year-old woman developed multiple compression fractures several years after a sleeve gastrectomy followed by pregnancy. Despite normal areal BMD values assessed by dual-energy X-ray absorptiometry and no family history of osteoporosis, the patient demonstrated low lumbar spine trabecular bone score, as well as low peripheral trabecular volumetric BMD and deterioration of trabecular microarchitecture assessed by high-resolution peripheral quantitative computed tomography. Women of reproductive age should be provided with lifestyle management targeting bone health following bariatric surgery.

Effects of calcium supplementation on circulating osteocalcin and glycated haemoglobin in older women Abstract Summary One year of calcium supplementation in older women led to modest reductions in total osteocalcin and undercarboxylated osteocalcin (ucOC), with no changes in muscle or fat mass, or glycated haemoglobin. Future studies should explore whether treatments with more profound effects of suppressing ucOC may lead to impaired glycaemic control. Introduction Total osteocalcin (TOC) is a marker of bone turnover, while its undercarboxylated form has beneficial effects on glucose metabolism in mice. This post hoc analysis of a randomised double-blind, placebo-controlled trial examined whether 1 year of calcium supplementation affected circulating TOC, undercarboxylated osteocalcin (ucOC) or glycated haemoglobin (HbA1c) in 1368 older community-dwelling women (mean age 75.2 ± 2.7 years). Methods Women enrolled in the Calcium Intake Fracture Outcome Study trial (1998–2003) were supplemented with 1.2 g/d of elemental calcium (in the form of calcium carbonate) or placebo. Circulating TOC, ucOC and HbA1c was measured at 1 year (1999). Results After 1 year of calcium supplementation, TOC and ucOC levels were 17% and 22% lower compared with placebo (mean 22.7 ± 9.1 vs. 27.3 ± 10.9 μg/L and 11.1 ± 4.9 vs. 13.0 ± 5.7 μg/L, both P < 0.001). Carboxylated osteocalcin/ucOC was 6% lower after calcium supplementation (P < 0.05). Despite this, no differences in HbA1c were observed (calcium, 5.2 ± 0.6 vs. placebo, 5.3 ± 0.8%; P = 0.08). Calcium supplementation did not affect BMI, whole body lean or fat mass. In exploratory analyses, total calcium (dietary and supplemental) was inversely related to TOC and ucOC, indicating calcium intake is an important dietary determinant of osteocalcin levels. Conclusion One year of calcium supplementation in older women led to modest reductions in TOC and ucOC, with no changes in muscle or fat mass, or HbA1c. Future studies should explore whether treatments with more profound effects of suppressing ucOC may lead to impaired glycaemic control.

Thoracic kyphosis assessment in postmenopausal women: an examination of the Flexicurve method in comparison to radiological methods Abstract Summary The Flexicurve ruler is an alternative method to radiographs for measuring thoracic kyphosis (curvature), but it is not certain that it is comparable. This study shows that Flexicurve can estimate radiographic vertebral centroid angles with less error than Cobb angles but that its accuracy would be inadequate for most clinical purposes. Introduction The Flexicurve ruler provides a non-radiological method of measuring thoracic kyphosis (TK) that has moderately strong correlations with the gold-standard radiographic Cobb angle method, while consistently underestimating the TK angle. Cobb angles can include measurement errors that may contribute to poor agreement, particularly in older populations. The vertebral centroid angle could be a better radiographic reference method for the validation of Flexicurve. Using two separate radiographic measurements of TK, we examined the validity of Flexicurve. We aimed to ascertain the level of agreement between measures and to empirically explore reasons for between-method differences. Methods TK angles determined using Flexicurve and radiographic Cobb and vertebral centroid methods were compared using data from 117 healthy postmenopausal women (mean (SD) age 61.4 (7.0) years). Bland and Altman plots were used to assess differences between methods. Age, bone mineral density and body mass index were examined as characteristics that might explain any differences. Results Flexicurve angles were scaled prior to analysis. There was no statistically significant difference between angles produced by Flexicurve and vertebral centroid methods (MD − 2.16°, 95%CI − 4.35° to 0.03°) although differences increased proportionally with TK angles. Flexicurve angles were significantly smaller than radiographic Cobb angles and depending on the scaling method used, systematic error ranged between − 2.48° and − 5.19°. Age accounts for some of the differences observed (R2 < 0.08, p < 0.005). Conclusions TK measured using the Flexicurve shows better agreement with the radiographic vertebral centroid method, but inaccuracy of the Flexicurve increases with increasing angle of kyphosis.