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Background Zoledronate prevents fractures in older women when administered every 12 to 18 months, but its effects on bone density and bone turnover persist beyond 5 years. Whether infrequent zoledronate administration would prevent vertebral fractures in early postmenopausal women is unknown. Methods We conducted a 10-year, prospective, double-blind, randomized, placebo-controlled trial involving early postmenopausal women (50 to 60 years of age) with bone mineral density T scores lower than 0 and higher than −2.5 (scores of −1 or higher typically indicate normal bone mineral density) at the lumbar spine, femoral neck, or hip. Participants were randomly assigned to receive an infusion of zoledronate at a dose of 5 mg at baseline and at 5 years (zoledronate–zoledronate group), zoledronate at a dose of 5 mg at baseline and placebo at 5 years (zoledronate–placebo group), or placebo at both baseline and 5 years (placebo–placebo group). Spinal radiographs were obtained at baseline, 5 years, and 10 years. The primary end point was morphometric vertebral fracture, which was assessed semi quantitatively and defined as at least a 20% change in vertebral height from that seen on the baseline radiograph. Secondary end points were fragility fracture, any fracture, and major osteoporotic fracture. Of 1054 women with a mean age of 56.0 years at baseline, 1003 (95.2%) completed 10 years of follow-up. A new morphometric fracture occurred in 22 women (6.3%) in the zoledronate-zoledronate group, in 23 women (6.6%) in the zoledronate- placebo group, and in 39 women (11.1%) in the placebo-placebo group (relative risk, zoledronate- zoledronate vs. placebo-placebo, 0.56 [95% confidence interval (CI), 0.34 to 0.92; P=0.04]; and zoledronate-placebo vs. placebo-placebo, 0.59 [95% CI, 0.36 to 0.97; P=0.08]). The relative risk of fragility fracture, any fracture, and major osteoporotic fracture was 0.72 (95% CI, 0.55 to 0.93), 0.70 (95% CI, 0.56 to 0.88), and 0.60 (95% CI, 0.42 to 0.86), respectively, when zoledronate-zoledronate was compared with placebo-placebo and 0.79 (95% CI, 0.61 to 1.02), 0.77 (95% CI, 0.62 to 0.97), and 0.71 (95% CI, 0.51 to 0.99), respectively, when zoledronate-placebo was compared with placebo- placebo Ten years after trial initiation, zoledronate administered at baseline and 5 years was effective in preventing morphometric vertebral fracture in early postmenopausal women. [ABSTRACT FROM AUTHOR]

In a 2015 study of SQSTM1 mutation carriers who had initial negative bone scintigraphy, we found that the rate of development of Paget's disease of bone (PDB) over 5 yr was low. We report here an additional 8-yr follow-up of this cohort, exploring the hypothesis that the rate of development of PDB would increase as the cohort aged. In the current study, 21 of 24 subjects from 2015 who had a negative bone scintiscan at baseline and at first follow-up, had a repeat scintiscan and measurement of total serum alkaline phosphatase activity. Two subjects with P392L mutations were identified as having PDB (monostotic in one case, 2 bones involved in the other), giving an incidence during this follow-up period of 1 per 87 patient years or 11.9 per 1000 patient years. This was contrary to our hypothesis, as the rate of development had decreased as the cohort aged. When we compared by survival analysis the age at presentation with symptomatic PDB in the older generation, we found that the age of onset was later and disease severity in the affected relatives was markedly less than in their clinically affected parents (p  < .001). Our results are in keeping with other recently published studies and the general secular trend in PDB and support the idea that an important environmental-genetic interaction is involved with the development of PDB and that exposure to the putative environmental factor has substantially reduced. [ABSTRACT FROM AUTHOR]

Trustworthy literature is an essential part of knowledge, evidence-based information, and science. However, publications can contain mistakes or have results from unreliable research, which may compromise their integrity. In this review, we discuss publication integrity, with a focus on our field of biomedicine, and how it could be improved. In our experience, compromised publication integrity is frequently poorly handled, and we, and others, have reported that responses to publication integrity concerns can be inefficient, inconsistent, slow, opaque, and incomplete. Checklists and tools are now available to assist in the assessment of publication integrity, but systemic changes are needed. However, this requires many of the key parties involved (journals, publishers, institutions, academic societies, and regulators) to acknowledge and engage with the problem. There is little evidence of a willingness to do this. We conclude that it has been recognised for many years that the system for dealing with publication integrity is broken, but currently, there appears little interest in trying to improve it. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Design, Measurement and Patients Results Conclusion Vitamin D deficiency (VDD) in children can cause hypocalcaemia and rickets, but the prevalence of these complications and the 25‐hydroxyvitamin D (25OHD) concentrations below which they arise is uncertain. We investigated this in children (< 18 years) with 25OHD measurements.We obtained 25OHD results from the regional laboratory database, alongside albumin‐adjusted serum calcium (aCa), parathyroid hormone (PTH) and alkaline phosphatase (ALP) within 6 months of the index 25OHD. We defined confirmed VDD with biochemical abnormalities (VDDba) as all of low aCa, elevated PTH and elevated ALP. Possible/potential VDDba were defined as 2/3 VDDba criteria with the third test missing (possible), or in the normal range (potential). Clinical records of identified cases were reviewed, and a consensus diagnosis was reached.A total of 30,663 25OHD measurements were identified over 11.5 years (1 January 2009 to 15 June 2020); mean age 8 y, 47% female. After excluding ineligible results, 12,858 25OHD measurements from 9516 individuals with ≥ 2 aCa, PTH and ALP were analysed. Median 25OHD was 61 nmol/L; 36% < 50 nmol/L, 10% < 25 nmol/L. In total, 152 index 25OHD measurements were categorised as VDDba (30 confirmed, 23 possible and 99 potential). Following record review, 118 individuals (111 < 3 years) had 120 clinically confirmed VDDba episodes (62 clinical rickets, 15 biochemical rickets, 16 hypocalcaemia, 23 secondary hyperparathyroidism and 4 partially treated rickets). Fifty‐six had undetectable 25OHD, and 104 < 25 nmol/L. The proportion of clinically confirmed VDDba was 0.9% for all eligible 25OHD measurements, and 8% for 25OHD < 25 nmol/L.VDDba is uncommon in children undergoing 25OHD testing, and occurs almost entirely in children < 3 years. [ABSTRACT FROM AUTHOR]

Expressions of concern (EoC) can reduce the adverse effects of unreliable publications by alerting readers to concerns about publication integrity while assessment is undertaken. We investigated the use of EoC for 463 publications by two research groups for which we notified concerns about publication integrity to 142 journals and 44 publishers between March 2013 and February 2020. By December 2021, 95 papers had had an EoC, and 83 were retracted without an EoC. Median times from notification of concerns to EoC (10.4mo) or retraction without EoC (13.1mo) were similar. Among the 95 EoCs, 29 (30.5%) were followed by retraction after a median of 5.4mo, none was lifted, and 66 (69.5%) remained in place after a median of 18.1mo. Publishers with >10 notified publications issued EoCs for 0–81.8% of papers: for several publishers the proportions of notified papers for which EoCs were issued varied considerably between the 2 research groups. EoCs were issued for >30% of notified publications of randomized clinical trials and letters to the editor, and <20% of other types of research. These results demonstrate inconsistent application of EoCs between and within publishers, and prolonged times to issue and resolve EoCs. [ABSTRACT FROM AUTHOR]

Too often, journal assessments of potentially unreliable research are superficial, opaque and prolonged. Changes to the guidance given by the Committee on Publication Ethics could tighten up the process. [ABSTRACT FROM AUTHOR]

Retracted clinical trials may be influential in citing systematic reviews and clinical guidelines. We assessed the influence of 27 retracted trials on systematic reviews and clinical guidelines (citing publications), then alerted authors to these retractions. Citing publications were randomized to up to three e-mails to contact author with/without up to two coauthors, with/without the editor. After one year we assessed corrective action. We included 88 citing publications; 51% (45/88) had findings likely to change if retracted trials were removed, 87% (39/45) likely substantially. 51% (44/86) of contacted citing publications replied. Including three authors rather than the contact author alone was more likely to elicit a reply (P = 0.03). Including the editor did not increase replies (P = 0.66). Whether findings were judged likely to change, and size of the likely change, had no effect on response rate or action taken. One year after e-mails were sent only nine publications had published notifications. E-Mail alerts to authors and editors are inadequate to correct the impact of retracted publications in citing systematic reviews and guidelines. Changes to bibliographic and referencing systems, and submission processes are needed. Citing publications with retracted citations should be marked until authors resolve concerns. [ABSTRACT FROM AUTHOR]