1 British Medical Bulletin, 2015, 115: doi: /bmb/ldv029 Advance Access Publication Date: 29 June 2015 Occurrence, management and outcomes of hip fractures in patients with Parkinson s disease Rebecca J. Critchley, Sameer K. Khan, *, Alison J. Yarnall, Martyn J. Parker, and David J. Deehan Department of Trauma and Orthopaedics, Newcastle upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, Tyne and Wear NE7 7DN, UK, Institute of Neuroscience, Clinical Ageing Research Unit, Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne, Tyne and Wear NE4 5PL, UK, and Department of Trauma and Orthopaedics, Peterborough and Stamford Hospitals NHS Foundation Trust, Peterborough, Cambridgeshire PE3 9GZ, UK *Correspondence address. Apartment 509, The Bar, St. James Gate, Newcastle upon Tyne NE1 4BA, UK. sameer. Accepted 12 May 2015 Abstract Introduction: Hip fractures can be debilitating, especially in patients with pre-existing Parkinson s disease; they have reportedly worse outcomes than non-parkinson s disease patients. Sources of data: A computerized literature search on PubMed, Medline, Embase, and CINAHL, supplemented by a manual search of related publications. Areas of agreement: Parkinson s disease patients were found to have significantly lower bone mineral density; higher incidence of falls and hip fractures; delays to receiving their Parkinson s disease medication and surgery; higher risk of pneumonia, urinary infection, pressure sores, post-operative mortality; surgical complications and sequelae, including failed fixation, dislocation, longer hospital stay, re-operation; and increased risk of contralateral hip fracture. Areas of controversy: Regain of mobility and return to previous residential status have been variably reported. Growing points: All Parkinson s disease patients should be screened and considered for primary prevention treatment. On admission with hip fractures, attention should be paid to avoid delays to medication, ensuring safe anaesthetic and timely surgery, and post-operative chest physiotherapy and mobilization. The Author Published by Oxford University Press. All rights reserved. For permissions, please
2 136 R. J. Critchley et al., 2015, Vol. 115 Research: Research is needed in minimizing the bone-resorptive effects of anti-parkinson s disease medication. Key words: Parkinson s disease, bone mineral density, falls, hip fractures Introduction The overall prevalence of Parkinson s disease in the UK has risen from 108/10 5 in 1982 to 128/10 5 in 2000 and is projected to rise to 162/10 5 by The annual incidence of hip fractures has similarly risen in the UK, from per year in 1990s to a projected by Both these trends reflect an ageing population living longer and are mirrored in reports worldwide. Patients with Parkinson s disease are more likely to have a lower bone mineral density (BMD) than the general population and are more prone to falls and hip fractures. 3 5 Short- and long-term outcomes in patients with Parkinson s disease following hip fracture are generally considered to be worse than patients without Parkinson s disease despite similar hospital experiences. 6 We therefore undertook a qualitative systematic review of the literature with the objective of assessing whether the above was supported by the literature and whether special considerations should be made during pre- and post-operative management. Methods Search strategy A computerized literature search was performed on the electronic databases PubMed, Medline, Embase and CINAHL. Eligibility criteria included all abstracts in English, pertaining to (Parkinson s, Parkinsons, Parkinson s disease, Parkinsonism, movement disorders, dyskinesia) and (hip fractures, neck of femur fractures, proximal femoral fractures, fractures) and (bone metabolism, bone health, osteoporosis) between 1970 and An initial search using the above phrases yielded 451 results, sourced from PubMed (n = 83), Medline (n = 41), EMBASE (n = 303) and CINAHL (n = 24). An additional nine papers were also identified through a manual review of the bibliographies of identified papers. Criteria for consideration and data extraction Two investigators (R.C., S.K.) screened these 460 titles (full-text articles and abstracts); 295 irrelevant publications and 68 duplications were removed. Full-text articles were obtained for 96 out of the 97 assessed titles and were reviewed by both investigators. The following were excluded: case reports (n = 2), studies describing prevalence and incidence only (n = 43) and studies evaluating risk factors for osteoporosis (n = 30). A total of 22 papers that dealt with outcomes in hip fracture patients with Parkinson s disease were included in the review. The PRISMA checklist was used (Fig. 1). Results Fracture risk calculation Parkinson s disease patients have a 2.2-fold increased risk of all fractures and a 3 to 4 times increased risk of hip fracture Yiannopoulou et al. 4 compared hip fracture patients with age-matched controls and found both groups had sizable proportions of previously undiagnosed Parkinsonism (91.8 and 86.7% respectively, P = 0.471). Parkinson s disease is being increasingly reported as an independent risk factor for hip fractures, with an argument for its inclusion as an independent predictor in fracture risk calculators (e.g. the Q fracture tool). 11 Shribman et al. 12 found the FRAX assessment tool (accessed via to be more beneficial than the Qfracture tool; they also recommended fracture risk assessment in patients who had fallen with either a Parkinson s disease diagnosis >5 years, bilateral walking aids or a history of previous fragility fractures. Conversely, Kerss and O Neill 13 found that the Qfracture risk scoring tool identified 19% more Parkinson s disease patients at risk of fragility fractures compared with the FRAX tool.
3 Hip fracture outcomes in Parkinsons disease, 2015, Vol Fig. 1 Search methodology. The focus on Parkinson s disease has led to a new algorithm published by Lyell et al. 14 Patients are assessed for Calcium and Vitamin D status, previous falls and fractures, Qfracture score, 10-year probability and age; patients scoring high in these four steps receive treatment with or without DEXA scan (Step 5) while low risk are re-assessed with the FRAX tool (Step 6). Somewhat controversially, they recommend that all women aged 75 years and men aged 80 years with Parkinson s disease should be prescribed bone protection, and in the cases of a past history of falls, all women aged 70 and men aged 75 be treated. Occurrence of hip fractures The incidence of hip fractures is variably reported in Parkinson s disease patients, 7,13,15,16 though it is certainly higher in people with Parkinson s disease compared with the general population; this is in the face of a paucity of osteoporosis screening. 4,8 Chen et al. 15 reported that hip fractures occurred more than twice as frequently in Parkinson s disease patients than in a control group (10.4 versus 4.1%, respectively) during their 8-year study period. Walker et al. in their population-based cohort study from the North East of England found the incidence of hip fractures in Parkinson s disease patients over 60 years old to be 2171/ compared with 551/ in those without Parkinson s disease (i.e. four times higher risk). 6 Bhattacharya et al. 17 also found a similar overrepresentation by a factor of four; compared with the population of prevalence among patients with hip fracture, the prevalence of PD was up to 4.48 times (95% confidence interval [CI]: 4.46, 4.49) more than predicted, and when adjusted for gender and age, it was 4.02 (95% CI: 4.00, 4.03). The occurrence might be gender-related. Benzinger et al. 9 found the fracture risk to be higher in the male Parkinson s disease population, while Melton et al. 8 identified females with dementia as the most at-risk subgroup. In the UK, analyses of over 3 million primary care patients identified a 2-fold [95% confidence interval 1.8, 2.4] hazard of hip fracture for women with Parkinson s disease and 3-fold [2.4, 3.8] for men, even after accounting for multiple independent risk factors. 14,18 It has been suggested that dopaminergic medications may themselves increase fracture risk: one study reported nearly twice the number of femur fractures in those on treatment 19 while earlier work demonstrated a possible dose-dependent risk of overall fractures and
4 138 R. J. Critchley et al., 2015, Vol. 115 of hip fractures with anti-parkinsonian drugs. 20 One putative mechanism is via increased homocysteine levels, which itself has been reported as fracture risk. 21 Fracture morphology Christodoulou et al. 22 found cervical (intracapsular) fractures to be commoner than extracapsular fractures in their study of 21 Parkinson s disease patients. Similarly, Fisher et al. 23 also reported intracapsular fractures to be more prevalent in those with Parkinson s disease (6.3 vs. 1.6%, P = 0.002). In a sample of Parkinson s disease fallers versus a control group of non- Parkinson s disease fallers, BMD levels assessed at three femoral sites were significantly lower in the patients who sustained trochanteric fractures than in those with cervical fractures of the hip. 24 Pre-injury residential and ambulatory status Patients with Parkinson s disease are less likely to be living independently pre-fracture. 25 Walker et al. 6 found a significantly higher proportion of Parkinson s disease hip fracture patients living in nursing or residential care, compared with non-parkinson s disease patients (41.4 vs. 21.2%; P = 0.01). syndrome. A multidisciplinary approach can help reduce these medication errors. 28 Anaesthetic management Parkinson s disease poses its own anaesthetic issues, including neck movement, airway management, respiratory impairment, hypotension, arrhythmias, gastroparesis, dysglycaemias, interval between doses, drug interactions and post-operative delirium. 29 The majority of hip fracture operations can be planned by giving the immediate pre- and post-op doses as close to the surgery as possible; for longer operations, a nasogastric tube can be placed for perioperative medication delivery. 30 Delay to surgery To date only one study has evaluated this as an outcome; Walker et al. reported comparable delays from A&E admission to surgery in Parkinson s disease vs. non-parkinson s disease hip fracture patients (median 20.3 hours vs hours; P =0.48). Additionally, the proportions of patients having surgery within 36 hours were not significantly different (92.9 vs. 88.8%; P = 0.49). 6 Medication errors on admission The medication history is not always readily available on admission with a hip fracture, and verbal and nonverbal communication difficulties, delirium or presence of dementia may complicate this further. Parkinson s disease patients often have personalized and precisely timed medication schedules, which might conflict with established drug round timings on the wards. 26 Up to 75% of acute medical and 25% of surgical (non-hip fracture) admissions in Parkinson s disease patients are associated with omission, alteration or mistiming of Parkinson s medication. 27 Hip fractures incur similar inadvertent pharmacomodulation, 28 and the vagaries of the trauma theatre lists and nil-by-mouth instructions further compound the problem. Its sequelae are serious and potentially life-threatening, including worsening rigidity, further injuries from falls, pressure sores, aspiration pneumonia and neuroleptic malignant Post-operative pneumonia Parkinson s disease s neuromuscular dysfunction leads to an obstructive respiratory pattern, which predisposes to atelectasis, retained secretions and pulmonary infection. Unsurprisingly, pneumonia is the leading cause of mortality among Parkinson s disease patients in the community and in hospital. 31 This holds true for Parkinson s disease patients with hip fractures, where further reduction in mobility in the perioperative period predisposes to aspiration pneumonia. Yuasa found pneumonia occurred in 8.6% of Parkinson s disease patients with fractures, compared with 1.2% in those without Parkinson s disease (P < 0.01). 32 A similarly high chest infection rate was reported by Staeheli et al. 33 (40%) and Eventov et al. 34 (43%). Chest physiotherapy and early mobilization are therefore essential in these patients.
5 Hip fracture outcomes in Parkinsons disease, 2015, Vol Urinary tract infections Bladder dysfunction is common in Parkinson sdisease patients 35 and urinary infections per se can account for up to 20% of all acute hospital admissions in community-dwelling Parkinson s disease patients. 36 Urinary infections are also among the most frequently reported medical complications after non-orthopaedic surgery 37 as well as elective hip arthroplasty. 38 About 20 23% of Parkinson s disease hip fractures suffer an infection during their admission. 33,34 Pressure sores Low skin turgor, reduced muscle mass, immobility, constant pressure and shear force or friction all contribute to development of pressure sores. 39 Parkinson s disease has been reported as contributing significantly to pressure sore development in both home-dwelling 40 and institutionalized patients. 39 Historically, Parkinson s disease patients with hip fractures have suffered significantly high rates of pressure sores. Coughlin and Templeton reported a rate of 49% in those that received an endoprosthesis for intracapsular fractures (n = 27), possibly explained by their patients being allowed to stand only after 1 week and to sit after 2 weeks of surgery (to reduce dislocations). 41 Such restrictions did not apply in Eventov et al. s 34 series published a few years later, where pressure sores occurred in 25% of patients. Walker et al. s recent study still reported 13.8% Parkinson s disease developing pressure sores after hip fracture surgery, compared with only 3.1% in those without Parkinson s disease (P = 0.001). 6 Risk of dislocation and failed fixation The rigidity in Parkinson s disease was historically cited as a reason to avoid hemiarthroplasty in intracapsular fractures. 42 Coughlin and Templeton reported a 37% dislocation rate. 41 The widespread uptake of Levodopa and other pharmacotherapy in the late 1970s and early 1980s 43 may have contributed to the declining dislocation rates in subsequently published papers. In 1988, Staeheli et al. 33 observed one dislocation in 50 implanted hemiarthroplasties performed through a variety of surgical approaches (anterolateral in 25, posterolateral in 20 and transtrochanteric in 5). Turcotte et al. 44 in 1990 reported 5 dislocations (10.6%) in their study with 47 posterior-approach hemiarthroplasties. Nonetheless, the relative dislocation rate seems to have remained constant, with both Whittacker et al. 45 and Hammer 46 reporting 3 to 4 times higher rates than in non-parkinson s disease patients. Walker found that the re-operation rate was four times that in Parkinson s disease patients with hip fractures (6.9 vs. 1.7%, P =0.4). 6 Similarly, Karadsheh et al. 47 have recently reported higher rates of dislocation, failed fixation and revision surgery in their cohortof141parkinson s disease hip fracture patients compared with 282 patients matched for age, gender, ASA and operation type. Post-operative rehabilitation Parkinson s disease patients tend to have a longer length of hospital stay following a hip fracture, with rehabilitation being much slower and less successful. 6,48,49 On discharge, patients are likely to be less independent and need some form of social help or higher level of care. 7,46,49 Only Frisina et al. 50 have found equivalent rehabilitation speed and success in both Parkinson s disease and non-parkinson s disease patients, provided it was performed in a highly specialized unit with a multidisciplinary team. Regain of mobility Regain of mobility is usually slower in Parkinson s disease patients in the initial post-operative period. 6,41,46 It steadily improves over the ensuing few months in the surviving patients, 33 and by 1 year the regain of mobility approached that in fracture patients without Parkinson s disease. 49 Gialanella found 62.5% of patients treated by hemiarthroplasty and 35.2% of those treated by internal fixation had recovered unassisted mobility by the end of their rehabilitation treatment. 51 Post-operative mortality Mortality following hip fractures in Parkinson s disease patients has been variably reported. While
6 140 R. J. Critchley et al., 2015, Vol. 115 some authors found similar 1-year mortality to non-parkinson s disease patients, 46,49,52 others have reported higher mortality, for example both Wieler et al. 7 and Harris-Hayes et al. 53 found a substantial increase in adjusted longer term mortality following hip fracture compared with their control group. This increase was most marked in males and African Americans, but lower among Hispanics. 53 Second hip fracture The occurrence of a second, contralateral, noncontemporaneous hip fracture has been reported to range from 6 to 12% in most studies; 54 however, this varies with the length of follow-up, increasing from 9% at 1 year to 20% at 5 years. 55 Parkinson s disease patients are reported to be at increased risk of a subsequent contralateral hip fracture. 4 Yamanashi et al. 56 found Parkinson s disease to be associated with a 3.2-fold increase in the risk of a second hip fracture. Discussion Special consideration should be given to reducing fracture risk in Parkinson s disease patients, in particular those with an at-risk medical or medication history. After assessment of fracture risk, patients should be considered for primary prevention treatment. On admission with hip fractures, attention should be focused on avoiding delays to medication, ensuring safe anaesthetic and timely surgery, and post-operative chest physiotherapy and mobilization. Parkinson s disease patients with hip fractures remain at higher risk of mortality, and surgical (failed surgery, dislocation, re-operation) and medical complications ( pneumonia, urinary infection, pressure sores). In survivors, long-term rehabilitation results can be poorer than or equivalent to non-parkinson s disease patients. A multidisciplinary approach with a geriatrician and a neurologist should be considered to reduce hospital stay and increase the chance of return to pre-fracture social status. Further research is needed in (i) minimizing inadvertent bone resorption with anti-parkinson s disease medication, (ii) ensuring compliance with bone protection medication and (iii) expediting safe surgery and perioperative anaesthesia in those sustaining fractures. With regards to fracture prevention, it should be noted that the majority of studies of treatments of osteoporosis have come from the same research group in Asia and are yet to be replicated, therefore may not be applicable to a Caucasian population. 57 The numbers within each treatment arm were relatively small, with computer x-ray densitometry used to measure BMD rather than dual-energy x-ray absorptiometry; the latter is the gold standard. In addition, treatment with oral bisphosphonates may be problematic if swallowing is an issue with Parkinson s disease patients and also with precise medication timings. Newer treatments such as subcutaneous denosumab or intravenous bisphosphonates may be suitable alternatives, although to date there is no specific evidence for their use in Parkinson s disease populations. Conflict of Interest statement The authors do not have any conflict of interests to declare. References 1. Parkinson s UK. Parkinson s prevalence in the United Kingdom default/files/parkinsonsprevalenceuk_0.pdf (15 December 2014, date last accessed). 2. White SM, Griffiths R. Projected incidence of proximal femoral fracture in England: a report from the NHS Hip Fracture Anaesthesia Network (HIPFAN). Injury 2011; 42: Abou-Raya S, Helmii M, Abou-Raya A. Bone and mineral metabolism in older adults with Parkinson s disease. Age Ageing 2009;38: Yiannopoulou KG, Papageorgiou SG, Anastasiou IP, et al. Prevalence of Parkinsonism in older patients with hip fracture. Hip Int 2011;21: Invernizzi M, Carda S, Viscontini GS, et al. Osteoporosis in Parkinson s disease. Parkinsonism Relat Disord 2009; 15: Walker RW, Chaplin A, Hancock RL, et al. Hip fractures in people with idiopathic Parkinson s disease: incidence and outcomes. Mov Disord 2013;28: Wieler M, Jones CA, Martin WRW, et al. Incidence of hip fracture in Parkinson disease: a population-based
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