Clinical Features, Incidence and Treatment Outcome in Pregnancy-Associated Osteoporosis: A Single-Centre Experience over Two Decades.

Pregnancy-associated osteoporosis (PAO) is a rare syndrome which typically presents with vertebral fractures during pregnancy or lactation. The medical records of sixteen patients with PAO who presented to a specialist clinic at the Western General Hospital in Edinburgh over a 20-year period were reviewed to evaluate the mode of presentation, potential risk factors and response to treatment. The most common presentation was back pain occurring in 13/16 (81.2%) individuals due to multiple vertebral fractures. The diagnosis was usually made postpartum and in 12/16 individuals (75.0%), PAO presented during the woman's first pregnancy. Medicines which could have contributed to the development of PAO included thromboprophylaxis therapies in 8 subjects (50.0%), inhaled or injected corticosteroids in 5 (31.3%), anticonvulsants in 2 (12.5%) and a LHRH agonist in 1 (6.3%). Five individuals reported a family history of osteoporosis, and two pregnancies were complicated by hyperemesis gravidarum. Treatments administered included calcium and vitamin D supplements, bisphosphonates and teriparatide. Bone mineral density increased following the diagnosis in all cases, regardless of treatment given. One patient had further fracture during follow-up, but four patients had subsequent pregnancies without fractures. We estimated that in this locality, the incidence of PAO was 6.8/100,000 pregnancies with a point prevalence of 4.1 per 100,000 women. This case series indicates the importance of family history of osteoporosis and thromboprophylaxis drugs as risk factors for PAO while also demonstrating that the reductions in bone density tend to reverse with time, irrespective of the treatment given.

Effective Communication and the Osteoporosis Care Gap.

Many pharmacological treatments are now available to prevent the occurrence of fragility fractures in patients with osteoporosis. Despite this, concerns persist that many individuals who might benefit from osteoporosis treatment do not receive it-the "osteoporosis treatment gap." The underlying reasons for this gap are diverse and include those who are not identified as being eligible for treatment as well as those who intentionally choose not to take medications because of uncertainty, unanswered questions, or an inability to understand or do what is being asked of them. In this perspective article we highlight the importance of providing information on the causes and consequences of osteoporosis during encounters when treatment is being discussed as well as what osteoporosis treatment can achieve and what it cannot. We also review the importance of communicating the benefits and risks of treatment in absolute terms so that patients can understand what taking treatment will mean for them and discuss the utility of decision aids to assist in these conversations. We suggest it is not the treatment gap that is the problem but the care gap. This language acknowledges the importance of healthcare providers identifying those likely to benefit from treatment and increasing the quality of clinical conversations to promote patient engagement and involvement while respecting that treatment is not suitable or wanted by all. © 2022 American Society for Bone and Mineral Research (ASBMR).

Tocilizumab for the treatment of giant cell arteritis in Scotland: a report on behalf of the Scottish Society for Rheumatology standards subgroup.

Objectives: The aim was to describe a modern National Health Service (NHS) Scotland cohort of patients with GCA over 12 months of care to include clinical presentation, practices relating to assessment and treatment, and specifically, the use of tocilizumab. Methods: A multicentre audit of patients newly diagnosed with GCA between November 2019 and October 2021 was established on behalf of the Scottish Society for Rheumatology. Clinical data were collected retrospectively by rheumatology teams at participating NHS centres using electronic patient records. An extended cohort of patients from NHS Lothian was examined to investigate outcomes of tocilizumab use for >1 year. Results: Sixty-three patients from three NHS Scotland health boards were included, with analysis of data from 216 clinic episodes. Mean follow-up was 371 days. Mean age was 71 years; 62% were female. The most common presenting features were headache (93.6%), scalp tenderness (82.5%) and ocular symptoms (24%). At baseline, 63% of patients had at least one existing risk factor for adverse outcomes from high-dose CS use, namely hypertension (57.1%), diabetes (24%) and osteoporosis (11%). Thirty per cent of all patients (19 of 63) received tocilizumab, with only 11% (7 of 63) receiving tocilizumab owing to glucocorticoid risk factors at baseline. One-quarter of all patients (16 of 63) experienced relapse of GCA during follow-up, of whom six were subsequently treated with tocilizumab. Conclusion: This multicentre audit demonstrates that despite its availability for patients with risk factors for CS adversity and those who suffer relapse of GCA, tocilizumab is used in less than one-quarter of patients who might benefit. The reasons for this require further exploration.

Corrigendum: When to Start and Stop Bone-Protecting Medication for Preventing Glucocorticoid-Induced Osteoporosis.

[This corrects the article DOI: 10.3389/fendo.2021.782118.].

The Impact of High Dose Glucocorticoids on Bone Health and Fracture Risk in Systemic Vasculitides.

Systemic vasculitides are a range of conditions characterized by inflammation of blood vessels which may manifest as single organ or life-threatening multisystem disease. The treatment of systemic vasculitis varies depending on the specific disease but historically has involved initial treatment with high dose glucocorticoids alone or in conjunction with other immunosuppressive agents. Prolonged glucocorticoid treatment is frequently required as maintenance treatment. Patients with small and large vessel vasculitis are at increased risk of fracture. Osteoporosis may occur due to intrinsic factors such as chronic inflammation, impaired renal function and to a large extent due to pharmacological therapy with high dose glucocorticoid or combination treatments. This review will outline the known mechanism of bone loss in vasculitis and will summarize factors attributing to fracture risk in different types of vasculitis. Osteoporosis treatment with specific consideration for patients with vasculitis will be discussed. The use of glucocorticoid sparing immunosuppressive agents in the treatment of systemic vasculitis is a significant area of ongoing research. Adjunctive treatments are used to reduce cumulative doses of glucocorticoids and therefore may significantly decrease the associated fracture risk in patients with vasculitis. Lastly, we will highlight the many unknowns in the relation between systemic vasculitis, its treatment and bone health and will outline key research priorities for this field.

Communicating Absolute Fracture Risk Reduction and the Acceptance of Treatment for Osteoporosis.

Healthcare professionals frequently communicate the benefits of treatments as a relative risk reduction (RRR) in the likelihood of an event occurring. Here we evaluated whether presenting the benefits of osteoporosis treatment as a RRR in fractures compared with an absolute risk reduction (ARR) changed the patient's attitudes towards accepting treatment. We surveyed 160 individuals attending a specialised osteoporosis clinic for face-to-face consultations between May 2018 and Jan 2021. They were presented with information on RRR for the treatment being considered followed by ARR and after each question were asked about how likely they would be to start treatment on a 5-point scale (1 = very likely, 5 = very unlikely). Participants were less likely to accept treatment when it was presented as ARR (mean score 2.02 vs. 2.67, p < 0.001, 95% CI for difference - 0.82 vs - 0.47) and thirty-eight participants (23.7%) declined treatment with knowledge of their ARR when they would have accepted the same treatment based on the RRR. Individuals who declined treatment had a lower 5-year risk of fracture than those who accepted treatment (9.0 vs. 12.5%, p < 0.001, 95% CI - 5.0 to - 1.6) and as fracture risk decreased, the participant was less likely to accept treatment (Spearman r - 0.32, 95% CI - 0.46 to - 0.17, p ≤ 0.001). Whilst presentation of data as ARR more accurately reflects individual benefit and helps facilitate shared decision-making, clinicians should be aware that this will lead to a proportion of patients with lower fracture risk declining treatment for osteoporosis.

Evaluation of supported self-management in gout (GoutSMART): a randomised controlled feasibility trial.

BACKGROUND: Improved outcomes for patients with gout are associated with the control of urate levels; yet, less than 40% of patients in the UK are currently offered urate lowering therapy, and it is typically offered without titration to target. Supported self-management has been shown to benefit patients with chronic health conditions; therefore, we aimed to determine whether a supported gout self-management approach, incorporating treatment-to-target urate, helped participants reach target urate levels. METHODS: In this randomised controlled feasibility study, conducted in one hospital in Edinburgh, UK, we included patients (aged ≥18 years) with gout and a physician recommendation for initiation or escalation of urate lowering therapy. We randomised participants in a 2:1 ratio to a supported self-management group or a usual care group using the GoutSMART smartphone app. Participants in the self-management group were given a urate self-testing meter and received direct advice from clinicians on escalation of urate lowering therapy through the app. Participants were identified following referral to rheumatology, or using the Scottish Health Research Register, and they were screened and offered a detailed management plan before randomisation. Participants in the usual care group had a limited version of the app, which only allowed it to function as a health diary, and their gout management plan was implemented by their general practitioner. The primary outcome was the percentage of participants achieving a urate target of 0·30 mmol/L or less at 24 weeks, and analysis was by intent to treat. The trial was registered with ClinicalTrials.gov, NCT03274063, and there is an extension study ongoing. There was no masking of participants or assessors. FINDINGS: Between April 5, 2019, and March 19, 2020, 60 (65%) of 92 patients screened were enrolled to the study. The mean age was 52.8 years (SD 14.6); 56 (93%) of the participants were male, and 4 (7%) were female. 58 (97%) of participants were White. 40 participants were assigned to the self-supported management group and 20 participants were assigned to the usual care group. A urate target of 0·30 mmol/L or less at 24 weeks was reached by 29 (73%) participants in the supported self-management group compared with 3 (15%) participants in the usual care group (risk difference 0·58 [95% CI 0·37-0·78]; p<0·0001). 90% of participants completed the study with no difference in the drop-out rate or adverse events between the two groups. INTERPRETATION: Supported self-management of gout results in substantially improved attainment of urate targets compared with usual care, and it is well tolerated. Larger trials will be needed to fully evaluate the clinical and cost-effectiveness of this approach. FUNDING: Edinburgh & Lothians Health Foundation.

Review of Current Real-World Experience with Teriparatide as Treatment of Osteoporosis in Different Patient Groups.

Teriparatide has proven effective in reducing both vertebral and non-vertebral fractures in clinical trials of post-menopausal and glucocorticoid-induced osteoporosis. Widespread adoption of Teriparatide over the last two decades means that there is now substantial experience of its use in routine clinical practice, which is summarized in this paper. Extensive real-world experience of Teriparatide in post-menopausal osteoporosis confirms the fracture and bone density benefits seen in clinical trials, with similar outcomes identified also in male and glucocorticoid-induced osteoporosis. Conversely, very limited experience has been reported in pre-menopausal osteoporosis or in the use of Teriparatide in combination with other therapies. Surveillance studies have identified no safety signals relating to the possible association of Teriparatide with osteosarcoma. We also review the evidence for predicting response to Teriparatide in order to inform the debate on where best to use Teriparatide in an increasingly crowded therapeutic landscape.

When to Start and Stop Bone-Protecting Medication for Preventing Glucocorticoid-Induced Osteoporosis.

Glucocorticoid-induced osteoporosis (GIOP) leads to fractures in up to 40% of patients with chronic glucocorticoid (GC) therapy when left untreated. GCs rapidly increase fracture risk, and thus many patients with anticipated chronic GC exposures should start anti-osteoporosis pharmacotherapy to prevent fractures. In addition to low awareness of the need for anti-osteoporosis therapy among clinicians treating patients with GCs, a major barrier to prevention of fractures from GIOP is a lack of clear guideline recommendations on when to start and stop anti-osteoporosis treatment in patients with GC use. The aim of this narrative review is to summarize current evidence and provide considerations for the duration of anti-osteoporosis treatment in patients taking GCs based on pre-clinical, clinical, epidemiologic, and pharmacologic evidence. We review the pathophysiology of GIOP, outline current guideline recommendations on initiating and stopping anti-osteoporosis therapy for GIOP, and present considerations for the duration of anti-osteoporosis treatment based on existing evidence. In each section, we illustrate major points through a patient case example. Finally, we conclude with proposed areas for future research and emerging areas of interest related to GIOP clinical management.

Assessment of pesticide inputs into surface waters by agricultural and urban sources - A case study in the Querne/Weida catchment, central Germany.

Pesticide inputs into surface waters may cause harmful effects on aquatic life communities and substantially contribute to environmental pollution. The present study aimed at evaluating the input pathways in the Querne/Weida catchment (central Germany) to efficiently target mitigation measures of pesticide losses. Relevant pesticide substances were measured in surface waters in agricultural and urban surroundings and in soil samples within the catchment area. Pesticides application data from farmers were analyzed. Additionally, batch tests were performed to determine sorption and degradation of relevant pesticides for site specific soil properties. Frequency of detection, number of pesticides and maximum concentrations were much higher in the surface water samples in mainly urban surroundings compared to those in agricultural surrounding. The most frequently detected substances were glyphosate, AMPA, diflufenican and tebuconazole in surface water samples and diflufenican, boscalid, tebuconazole and epoxiconazole in the topsoil samples. Glyphosate and AMPA contributed to the highest concentrations in surface water samples (max. 58 µg L-1) and soil samples (max. 0.19 mg kg-1). In most cases, pesticide detections in surface water and soil were not consistent with application data from farmers, indicating that urban sources may affect water quality in the catchment area substantially. However, it was observed that pesticide substances remain in the soil over a long time supported by sorption on the soil matrix. Therefore, delayed inputs into surface waters could be suspected. For the implementation of reduction measures, both urban and agricultural sources should be considered. Novel findings of the study: pesticide detections were not consistent with application data from farmers, urban sources contributed substantially to pesticide pollution of surface waters.

The Role of Autoantibodies in Bone Metabolism and Bone Loss.

Many autoimmune diseases are associated with deranged bone metabolism. The resulting localized or systemic bone loss can compromise the quality of life of patients by causing local bone deformities or fragility fractures. There is emerging evidence that antibodies have a direct impact on key players of bone homeostasis, in particular osteoclasts. Clinical and pre-clinical studies provide insight into the function of autoantibodies related to Rheumatoid Arthritis (rheumatoid factor, anti-citrullinated protein antibodies, and anti-carbamylated protein antibodies) and their inflammation-independent interaction with bone cells. Furthermore, we summarize the current knowledge about neutralizing antibodies to the antiresorptive protein osteoprotegerin, which have been described in patients with Coeliac Disease, Rheumatoid Arthritis, and Spondyloarthritis.

Autoantibodies to Osteoprotegerin are Associated with Low Hip Bone Mineral Density and History of Fractures in Axial Spondyloarthritis: A Cross-Sectional Observational Study.

Osteoporosis is a recognised complication of axial spondyloarthritis (axSpA) and is thought to be due to functional impairment and the osteoclast-activating effects of proinflammatory cytokines. The development of autoantibodies to OPG (OPG-Ab) has been associated with severe osteoporosis and increased bone resorption in rheumatoid arthritis. In this study, we screened for the presence of OPG-Ab in axSpA and reviewed their clinical significance. We studied 134 patients, recruited from two centres in the United Kingdom. Their mean age was 47.5 years and 75% were male. Concentrations of OPG-Ab were related to bone mineral density (BMD) and fracture history using linear and logistic regression models adjusting for age, gender, disease duration and activity, body mass index and bisphosphonate use. We detected OPG-Ab in 11/134 patients (8.2%). Femoral neck and total hip BMD were significantly reduced in OPG-Ab positive patients (0.827 vs. 0.967 g/cm2, p = 0.008 and 0.868 vs. 1.028 g/cm2, p = 0.002, respectively). Regression analysis showed that the presence of OPG-Ab was independently associated with total hip osteopenia (ORadj 24.2; 95% CI 2.57, 228) and history of fractures (ORadj 10.5; 95% CI 2.07, 53.3). OPG-Ab concentration was associated with total hip BMD in g/cm2 (ß = -1.15; 95% CI -0.25, -0.04). There were no associations between OPG-Ab concentration and bone turnover markers, but free sRANKL concentrations were lower in OPG-Ab-positive patients (median 0.04 vs. 0.11 pmol/L, p = 0.050). We conclude that OPG-Ab are associated with hip BMD and fractures in axSpA suggesting that they may contribute to the pathogenesis of bone loss in some patients with this condition.

Characterisation of osteoprotegerin autoantibodies in coeliac disease.

Autoantibodies neutralising the effect of the bone regulatory cytokine osteoprotegerin (OPG) have been described in a patient with severe osteoporosis and coeliac disease. This study aimed to determine the prevalence and epitope specificity of autoantibodies to OPG in patients with coeliac disease, and correlate their presence with bone mineral density. A direct enzyme-linked immunosorbent assay was developed and used to screen patients with coeliac disease for autoantibodies to OPG. Recombinant fragments of OPG were made to evaluate the epitope specificity and affinity of these antibodies. Phenotype information of the patients was obtained by case note review. Raised titres of antibodies to OPG were found in 7/71 (9.8 %) patients with coeliac disease, compared with 1/72 (1.4 %) non-coeliac osteoporosis clinic control patients (p < 0.05). Our results suggest that a polyclonal antibody response to OPG is raised in these patients capable of recognising different epitopes of OPG with varying affinity. The titre of OPG antibodies was associated with lower bone mineral density Z-score of the hip in coeliac patients on univariate (p < 0.05) and multivariate analysis including age, sex height and weight as covariates (p < 0.01). Polyclonal antibodies to OPG are more common in patients with coeliac disease and are independently associated with lower bone mineral density Z-scores of the hip. Further work is required to establish the clinical utility of testing for OPG antibodies.