Incidence of fractures in people with intellectual disabilities over the life course: a retrospective matched cohort study.

Background: Current osteoporosis guidelines do not identify individuals with intellectual disabilities (ID) as at risk of fracture, potentially missing opportunities for prevention. We aimed to assess the incidence of fractures in people with ID over the life course. Methods: Descriptive analysis of open cohort study using anonymised electronic health records from the UK Clinical Practice Research Datalink, linked to the Hospital Episode Statistics database (Jan 1, 1998-Dec 31, 2017). All individuals with ID were matched on age and sex to five individuals without ID.  We calculated the incidence rate (95% CI) per 10000 person-years (py) and incidence rate ratio (IRR, 95% CI) to compare fractures between individuals with and without ID (age 1-17 and ≥18 years) for any fracture, and in those aged 18-49 and ≥ 50 years for major osteoporotic fracture (vertebra, shoulder, wrist, hip), and for hip fracture. Findings: 43176 individuals with ID (15470 children aged 1-17 years; 27706 adults aged ≥ 18 years) were identified and included (40.4% females) along with 215733 matched control individuals.  The median age at study entry was 24 (10th-90th centiles 3-54) years. Over a median (10th-90th centile) follow-up of 7.1 (0.9-17.6) and 6.5 (0.8-17.6) years, there were 5941 and 24363 incident fractures in the ID and non ID groups respectively. Incidence of any fracture was 143.5 (131.8-156.3) vs 120.7 (115.4-126.4)/10000 py (children), 174.2 (166.4-182.4)/10000 py vs 118.2 (115.3-121.2)/10000 py (adults) in females. In males it was 192.5 (182.4-203.2) vs 228.5 (223.0-234.1)/10000 py (children), 155.6 (149.3-162.1)/10000 py vs 128.4 (125.9-131.0)/10000 py (adults). IRR for major osteoporotic fracture was 1.81 (1.50-2.18) age 18-49 years, 1.69 (1.53-1.87) age ≥ 50 years in women. In men it was 1.56 (1.36-1.79) age 18-49 years, 2.45 (2.13-2.81) age ≥ 50 years. IRR for hip fracture was 7.79 (4.14-14.65) age 18-49 years, 2.28 (1.91-2.71) age ≥ 50 years in women. In men it was 6.04 (4.18-8.73) age 18-49 years, 3.91 (3.17-4.82) age ≥ 50 years. Comparable rates of major osteoporotic fracture and of hip fracture occurred approximately 15 and 20 years earlier respectively in women and 20 and 30 years earlier respectively in men with ID than without ID. Fracture distribution differed profoundly, hip fracture 9.9% vs 5.0% of any fracture in adults with ID vs without ID. Interpretation: The incidence, type, and distribution of fractures in people with intellectual disabilities suggest early onset osteoporosis. Prevention and management strategies are urgently required, particularly to reduce the incidence of hip fracture. Funding: National Institute for Health and Care Research.

Use and risk of side effects of antiresorptive medication in people with intellectual disabilities.

Background: Recent studies show that adults with intellectual disabilities (ID) have high incidence of major osteoporotic fracture, especially hip fracture. In those ≥ 50 years, women and men with ID have an approximately two and four times higher rate of hip fracture than women and men without ID. Increased awareness of osteoporotic fracture risk in ID may lead to wider use of antiresorptive drugs (bisphosphonates and denosumab) in this population. We aimed to compare, between people with and without ID, the incidence of 1) major side effects, namely medication related osteoporosis of the jaw (ONJ) and oesophagitis; 2) oral pathology, which can be a risk factor for ONJ. Methods: Exploratory study investigating safety of first line osteoporosis medication within the population of a previous study comparing fracture incidence in people with and without ID in the GOLD database of the Clinical Practice Research Datalink 1998-2017. Results: The percentage of people on antiresorptive drugs was identical in the ID and non ID group (1.4%). The number of individuals who developed ONJ and oesophagitis during the study was too low to allow an accurate estimate of incidence of the events and a comparison between the two groups. The incidence of any oral pathology was 119.31 vs 64.68/10000 person year in the ID vs non ID group. Conclusions: Medication related ONJ and oesophagitis are rare in people with and without ID. There is no reason based on our findings to use antiresorptives differently in people with ID as in the rest of the population. However, the potential for side effects of antiresorptives will inherently increase with wider use of these drugs. Given the higher incidence of oral pathology in people with ID, which could put them at higher risk of ONJ, precautions should be taken to prevent this complication by attention to oral health.

Fracture rates have recently been shown to be substantially higher in people with intellectual disabilities (ID). This finding is likely to lead to the wider use of bone strengthening (antiresorptive) agents in this group, namely bisphosphonates and denosumab. These drugs are effective at reducing the risk of fractures, but carry potential adverse effects. One of these is the rare but serious condition osteonecrosis of the jaw (ONJ). We studied general practice records to investigate whether the incidence of this problem is higher in people with ID taking these drugs. We also looked at the incidence of oral conditions that may put an individual at higher risk of it, including periodontitis, dental abscess, and tooth extractions. The recording of ONJ in people with ID was extremely low, no different from the general population in our study, although we were using general practice rather than dental records. However, dental problems that might predispose to it were recorded nearly twice as frequently in the group with ID. The other side effect we looked at was oesophagitis, which was not found to be more common in people with ID taking bisphosphonates. This study highlights the need to provide good oral hygiene, dental care and surveillance in people with ID receiving antiresorptive drug therapy.

Vitamin D deficiency in patients with intellectual disabilities: prevalence, risk factors and management strategies.

BACKGROUND: People with intellectual disabilities have a high risk of osteoporosis and fractures, which could partly be as a result of vitamin D deficiency. AIMS: To compare the serum vitamin D (25(OH)D) levels of 155 patients with intellectual disabilities under psychiatric care and 192 controls, investigate potential risk factors for vitamin D deficiency in people with intellectual disabilities and assess available treatments. METHOD: Cross-sectional observational study followed by treatment evaluation. Results Almost twice as many patients with intellectual disabilities had vitamin D deficiency (25(OH)D <50 nmol/l) compared with controls (77.3% v. 39.6%, P<0.0001). In the intellectual disabilities group, winter season (P<0.0001), dark skin pigmentation (P<0.0001), impaired mobility (P = 0.002) and obesity (P = 0.001) were independently associated with lower serum 25(OH)D. In most patients, 800 IU colecalciferol daily normalised 25(OH)D levels. CONCLUSIONS: Vitamin D deficiency is highly prevalent in people with intellectual disabilities, partly because of insufficient exposure to sunlight. Screening and treatment strategies, aiming to reduce these patients' high fracture risk, should be introduced. Similar strategies may be required in other psychiatric populations at risk for fractures and with a tendency to spend excessive time indoors.

Safety of antipsychotics in people with intellectual disability.

BACKGROUND: Despite frequent use, little is known about the metabolic and endocrine side-effects of antipsychotics in individuals with intellectual disability. AIMS: To compare indices of obesity, glucose, lipids and prolactin between antipsychotic-treated and antipsychotic-naive individuals with intellectual disability and also between participants with intellectual disability and controls from the general population. METHOD: Observational study comparing 138 antipsychotic-treated and 64 antipsychotic-naive participants with intellectual disability in one National Health Service trust with general population controls. RESULTS: Antipsychotic treatment comprised: risperidone 48%,olanzapine 18%, thioxanthenes 10%, other 24%; monotherapy 95% of participants; mean treatment duration 8 years;median daily chlorpromazine equivalent dose 108 mg(range 16­667). Metabolic indices were the same or more favourable in the intellectual disability group than the general population control group but overweight/obesity and type 2 diabetes were more prevalent in the women in the intellectual disability group than the control group. Metabolic indices were similar, statistically or clinically, between the antipsychotic-treated and the antipsychotic-naive groups but there was a non-significant trend towards a higher rate of type 2 diabetes in the antipsychotic group. A total of 100%and 70% of participants on amisulpride/sulpiride and risperidone respectively had hyperprolactinaemia, with secondary hypogonadism in 77% and 4% of affected women and men. CONCLUSIONS: Antipsychotics, on average, did not increase metabolic risk,although the existence of a susceptible subgroup at risk of diabetes cannot be excluded. Some antipsychotics induced hyperprolactinaemic hypogonadism, requiring active management. However, our findings suggest that antipsychotics at the low doses routinely prescribed for people with intellectual disability are generally safe in relation to metabolic adverse effects, even if efficacy remains poorly defined.

First United Kingdom Heart and Renal Protection (UK-HARP-I) study: biochemical efficacy and safety of simvastatin and safety of low-dose aspirin in chronic kidney disease.

BACKGROUND: Patients with chronic kidney disease are at increased risk for cardiovascular disease, but the efficacy and safety of simvastatin and aspirin are unknown in this patient group. METHODS: Patients were randomly assigned in a 2 x 2 factorial design to the administration of: (1) 20 mg of simvastatin daily versus matching placebo, and (2) 100 mg of modified-release aspirin daily versus matching placebo. RESULTS: Overall, 448 patients with chronic kidney disease were randomly assigned (242 predialysis patients with a creatinine level > or = 1.7 mg/dL [> or =150 micromol/L], 73 patients on dialysis therapy, and 133 patients with a functioning transplant). Compliance with study treatments was 80% at 12 months. Allocation to treatment with 100 mg of aspirin daily was not associated with an excess of major bleeds (aspirin, 4 of 225 patients [2%] versus placebo, 6 of 223 patients [3%]; P = not significant [NS]), although there was a 3-fold excess of minor bleeds (34 of 225 [15%] versus 12 of 223 patients [5%]; P = 0.001). Among those with predialysis renal failure or a functioning transplant at baseline, aspirin did not increase the number of patients who progressed to dialysis therapy (7 of 187 [4%] versus 6 of 188 patients [3%]; P = NS) or experienced a greater than 20% increase in creatinine level (63 of 187 patients [34%] versus 56 of 188 patients [30%]; P = NS). After 12 months of follow-up, allocation to 20 mg of simvastatin daily reduced nonfasting total cholesterol levels by 18% (simvastatin, 163 mg/dL [4.22 mmol/L] versus placebo, 196 mg/dL [5.08 mmol/L]; P < 0.0001), directly measured low-density lipoprotein cholesterol levels by 24% (89 mg/dL [2.31 mmol/L] versus 114 mg/dL [2.96 mmol/L]; P < 0.0001), and triglyceride levels by 13% (166 mg/dL [1.87 mmol/L] versus 186 mg/dL [2.10 mmol/L]; P < 0.01), but there was no significant effect on high-density lipoprotein cholesterol levels (2% increase; P = NS). Allocation to simvastatin therapy was not associated with excess risk for abnormal liver function test results or elevated creatine kinase levels. CONCLUSION: During a 1-year treatment period, simvastatin, 20 mg/d, produced a sustained reduction of approximately one quarter in low-density lipoprotein cholesterol levels, with no evidence of toxicity, and aspirin, 100 mg/d, did not substantially increase the risk for a major bleeding episode. Much larger trials are now needed to assess whether these treatments can prevent vascular events.