Surgically-treated Hip Fracture in older People. With Special Emphasis on Mortality Analysis

Hip fractures are associated with significant morbidity and mortality. Cervical and trochanteric fractures have a different morphometry, surgical treatment, and outcome. Polypharmacy, common in older people, is associated with increased mortality. The risk factors for mortality can be identified based on cause-of-death analysis. In this population-based study, 461 older, surgically in 1999-2000 treated hip fracture patients were enrolled. Incidence, morphometry, medication, mortality, and cause-of-death were analysed. Hip fractures were most commonly sustained by women, occurred mostly indoors, and often in institutions. One in four patients had sustained a previous fracture. Routine clinical radiographs revealed no differences in the hip geometry between hip fracture types. Age-adjusted mortality was higher in men than in women during the follow-up. Chronic lung disease and male sex were predictors of mortality after cervical fracture. In men, potent anticholinergics were associated with excess age-adjusted mortality. Men were more likely to die from circulatory disease and dementia after hip fracture than women. Mortality after hip fracture was 3-fold higher than that of the general population, including every cause-of-death class. Fracture prevention in institutions and homes, indoor safety measures, and treatment of chronic lung diseases should be encouraged. Hip morphometry analyses require more accurate measures than that provided by routine radiographs. Careful use of potent anticholinergics may reduce mortality. Compared to the general population, excess mortality after hip fracture was evident up to 9 years after hip fracture. Cause-of-death analysis indicates that all major comorbidities require optimal treatment after hip fracture surgery.

Fractures in older people - incidence, predictors and consequences

In older populations, fractures are common and the consequences of fractures may be serious both for an individual and for society. However, information is scarce about the incidence, predictors and consequences of fractures in population-based unselected cohorts including both men and women and a long follow-up. The objective of this study was to analyse the incidence and predictors of fractures as well as functional decline and excess mortality due to fractures, among 482 men and 695 women aged 65 or older in the municipality of Lieto, Finland from 1991 until 2002. In analyses, Poisson’s, Cox proportional Hazards and Cumulative Logistic regression models were used for the control of several confounding variables. During the 12-year follow-up with a total of 10 040 person-years (PY), 307 (26%) persons sustained altogether 425 fractures of which 77% were sustained by women. The total incidence of fractures was 53.4 per 1000 PY (95% confidence intervals [95% CI]: 47.9 - 59.5) in women and 24.9 per 1000 PY (95% CI: 20.4 - 30.4) in men. The incidence rates of fractures at any sites and hip fractures were associated with increasing age. No significant changes in the ageadjusted incidence rates of fractures were found in either gender during the 12-year follow-up. The predictors of fractures varied by gender. In multivariate analyses, reduced handgrip strength and body mass index (BMI) lower than 30 in women and a large number of depressive symptoms in men were independent predictors of fractures. A compression fracture in one or more thoracic or upper lumbar vertebras on chest radiography at baseline was associated with subsequent fractures in both genders. Lower body fractures independently predicted both short- (0-2 years) and long-term (up to 8 years) functional decline in mobility and activities of daily living (ADL) performance during the 8-year follow-up. Upper body fractures predicted decline in ADL performance during longterm follow-up. In the 12-year follow-up, hip fractures in men (Hazard Ratio [HR] 8.1, 95% CI: 4.4-14.9) and in women (HR 3.0, 95% CI: 1.9-4.9), and fractures at the proximal humerus in men (HR 5.4, 95% CI: 1.6-17.7) were independently associated with excess mortality. In addition, leisure time inactivity in physical exercise predicted independently both functional decline and excess mortality. Fractures are common among older people posing serious individual consequences. Further studies about the effectiveness of preventing falls and fractures as well as improving care and rehabilitation after fractures are needed.

Determinants of Bone Strength and Predictors of Hip Fracture among Finnish Adults. Results from the Health 2000 Survey and the Mini-Finland Health Survey

The objective of this thesis was to identify the determinants of bone strength and predictors of hip fracture in representative samples of Finnish adults. A secondary objective was to construct a simple multifactorial model for hip fracture prediction over a 10-year follow-up period. The study was based on the Health 2000 Survey conducted during 2000 to 2001 (men and women aged 30 years or over, n=6 035) and the Mini-Finland Health Survey conducted during 1978 to 1980 (women aged 45 years or over, n=2 039). Study subjects participated in health interviews and comprehensive health examination. In the Health 2000 Survey, bone strength was assessed by means of calcaneal quantitative ultrasound (QUS). The follow-up information about hip fractures was drawn from the National Hospital Discharge Register. In this study, age, weight, height, serum 25-hydroxyvitamin D (S-25(OH)D), physical activity, smoking and alcohol consumption as well as menopause and eventual HRT in women were found to be associated with calcaneal broadband ultrasound attenuation (BUA) and speed of sound (SOS). Parity was associated with a decreased risk of hip fracture in postmenopausal women. Age, height, weight or waist circumference, quantitative ultrasound index (QUI), S-25(OH)D and fall-related factors, such as maximal walking speed, Parkinson’s disease, and the number of prescribed CNS active medication were significant independent predictors of hip fracture. At the population level, the incremental value of QUS appeared to be minor in hip fracture prediction when the fall-related risk factors were taken into account. A simple multifactorial model for hip fracture prediction presented in this study was based on readily available factors (age, gender, height, waist circumference, and fallrelated factors). Prospective studies are needed to test this model in patient-based study populations.

Bearing-spesific complications of total hip arthroplasty: characterization and treatment

Hip resurfacing arthroplasty (HRA) and large head metal-on-metal total arthroplasty (LDH MoM THA) gained popularity during the last decade. Adverse reaction to metal debris (ARMD) is a unique complication of metal bearings. ARMD is a complex reaction caused by metal debris from metal-on- metal bearing surfaces and from trunnion corrosion of modular junctions. We analyzed survivorship of 8059 LDH MoM THAs based on data of the Finnish Arthroplasty Register. We found relatively high short-term survivorship for some LDH MoM THAs, but there were remarkable differences between the devices studied. After some alarming reports of failing MoM THAs, we studied the first 80 patients who had received a ReCap-M2a-Magnum implant at our institution and evaluated the prevalence of ARMD. We found a high prevalence of pseudotumors, and, because of this, we discontinued the use of MoM bearings and followed up all patients with a MoM THA. Bone loss due infection, osteolysis or fracture poses a great challenge for reconstructive and fracture surgery. Onlay allografting for both revision and fracture surgery provides mechanical stability and increases bone stock. Bone loss and implant stability must be assessed preoperatively and adequately classified; this provides guidelines for the operative treatment of periprosthetic fractures and revision THA. In our studies on structural allografts union rates were high, although the rates of infections and dislocations were marked. In summary, early results of the use of LDH MoM devices were encouraging. However, the survival of the LDH MoMs varied. The prevalence of adverse reaction to metal debris was high after application of the ReCap-Magnum THA. New implants should be introduced carefully and under close surveillance by University clinics and arthroplasty registers.

Patient-perceived health-related quality of life during recovery after total hip arthroplasty – a 6-month follow-up study

Potilaiden käsitys terveyteen liittyvästä elämänlaadusta lonkan tekonivelleikkauksen jälkeisenä toipumisaikana – kuuden kuukauden seurantatutkimus Tässä kaksivaiheisessa seurantatutkimuksessa tarkasteltiin potilaiden käsitystä terveyteen liittyvästä elämänlaadusta lonkan tekonivelleikkauksen jälkeisenä toipumisaikana. Tutkimuksen ensimmäisessä vaiheessa tarkoituksena oli sekä kuvailla potilaiden kokemuksia potilaana olosta, saamastaan hoidosta ja terveyspalveluorganisaatiosta että analysoida aikaisempien tutkimusten perusteella leikkauksen tuloksia potilaan kannalta. Toisessa vaiheessa tarkoituksena oli arvioida potilaiden kokemaa elämänlaatua leikkauksen jälkeen, ja sitä vaikuttivatko primaaritulokset (fyysinen toimintakyky, kipu, ahdistus) tai taloudelliset seuraukset (potilaiden itsensämaksamat kustannukset, palvelujen käyttö) terveyteen liittyvään elämänlaatuun. Tutkimuksen tavoitteena oli löytää mahdolliset kriittiset ajankohdat tai tekijät, jotka saattavat hidastaa toipumista ja siten huonontaa potilaiden elämänlaatua. Tätä tietoa voidaan käyttää hoitotyössä kun suunnitellaan sopivaa hoitoa ja tukea toipumisajalle. Tutkimuksen ensimmäisessä vaiheessa primaarileikkaukseen tulevat potilaat (n = 17) kuvailivat teemahaastatteluissa kokemuksiaan kahdesti leikkauksen jälkeen. Haastatteluaineisto analysoitiin induktiivisella sisällönanalyysilla. Lisäksi 17 tutkimusartikkelista analysoitiin deduktiivisella sisällönanalyysilla leikkauksen tuloksia potilaalle, tuloksiin vaikuttavia tekijöitä ja käytetyt tutkimusmetodit. Toisessa vaiheessa primaari- tai revisioleikkaukseen tulevat potilaat (n = 100) arvioivat leikkauksen tuloksia kuuden kuukauden ajan leikkauksen jälkeen: terveyteen liittyvää elämänlaatua, primaarituloksia ja taloudellisia seurauksia. Aineisto kerättiin erilaisilla mittareilla: Sickness Impact Profile, Finnish Version, Stait-Trait Anxiety Inventory, ja Numeric Rating Scale. Lisäksi käytettiin tätä tutkimusta varten tehtyjä kyselylomakkeita: Fyysinen toimintakyky-mittari, Palvelujen käyttö-mittari ja Kustannusmittari. Tutkimuksen toiseen vaiheen tulokset analysoitiin tilastollisilla menetelmillä. Potilaiden terveyteen liittyvä elämänlaatu parani ja kipu lievittyi leikkauksen jälkeen ja fyysinen toimintakyky lisääntyi toipumisaikana. Positiivisista muutoksista huolimatta potilaat kokivat ahdistusta samassa määrin kuin ennen leikkaustakin. Palvelujen käyttö vaihteli toipumisajan kuluessa ja potilaiden maksamissa kustannuksissa oli suuria vaihteluita. Fyysisen toimintakyvyn lisääntyminen ja kivun lieveneminen paransivat terveyteen liittyvää elämänlaatua. Sen sijaan huonompi elämänlaatu toipumisaikana oli yhteydessä suurempaan palvelujen käyttöön, kun taas kustannuksilla ei ollut yhteyttä elämänlaatuun. Potilaiden ominaispiirteet tulisi ottaa enemmän huomioon suunniteltaessa sopivaa leikkauksenjälkeistä hoitoa ja tukea. Potilaat tarvitsevat yksilöllisiä ohjeita, sillä monet taustatekijät (esim. ikä, sukupuoli, preoperatiivinen kipu, siviilisääty, ja leikkaustyyppi) vaikuttavat toipumiseen.

The Use of Radiostereometric Analysis in Fractures of the Distal Radius: From Phantom Models to Clinical Application

Radiostereometric analysis (RSA) is a highly accurate method for the measurement of in vivo micromotion of orthopaedic implants. Validation of the RSA method is a prerequisite for performing clinical RSA studies. Only a limited number of studies have utilised the RSA method in the evaluation of migration and inducible micromotion during fracture healing. Volar plate fixation of distal radial fractures has increased in popularity. There is still very little prospective randomised evidence supporting the use of these implants over other treatments. The aim of this study was to investigate the precision, accuracy, and feasibility of using RSA in the evaluation of healing in distal radius fractures treated with a volar fixed-angle plate. A physical phantom model was used to validate the RSA method for simple distal radius fractures. A computer simulation model was then used to validate the RSA method for more complex interfragmentary motion in intra-articular fractures. A separate pre-clinical investigation was performed in order to evaluate the possibility of using novel resorbable markers for RSA. Based on the validation studies, a prospective RSA cohort study of fifteen patients with plated AO type-C distal radius fractures with a 1-year follow-up was performed. RSA was shown to be highly accurate and precise in the measurement of fracture micromotion using both physical and computer simulated models of distal radius fractures. Resorbable RSA markers demonstrated potential for use in RSA. The RSA method was found to have a high clinical precision. The fractures underwent significant translational and rotational migration during the first two weeks after surgery, but not thereafter. Maximal grip caused significant translational and rotational interfragmentary micromotion. This inducible micromotion was detectable up to eighteen weeks, even after the achievement of radiographic union. The application of RSA in the measurement of fracture fragment migration and inducible interfragmentary micromotion in AO type-C distal radius fractures is feasible but technically demanding. RSA may be a unique tool in defining the progress of fracture union.

Potential of the Osteoclast’s Proton Pump as a Drug Target in Osteoporosis

Decreasing bone mass during aging predisposes to fractures and it is estimated that every second woman and one in five men will suffer osteoporotic fractures during their lifetime. Bone is an adaptive tissue undergoing continuous remodeling in response to physical and metabolic stimuli. Bone mass decreases through a net negative balance in the bone remodeling process of bone, in which the new bone incompletely replaces the resorbed bone mass. Bone resorption is carried out by the osteoclasts; the bone mineral is solubilized by acidification and the organic matrix is subsequently degraded by proteases. Several classes of drugs are available for prevention of osteoporotic fractures. They act by different mechanisms to increase bone mass, and some of them act mainly as antiresorptives by inhibition of osteoclast formation or their function. Optimally, a drug should act selectively on a specific process, since other processes affected usually result in adverse effects. The purpose of this study was to evaluate whether the osteoclastic vacuolar adenosine trisphosphatases (V-ATPase), which drives the solubilization of bone mineral, can be selectively inhibited despite its ubiquitous cellular functions. The V-ATPase is a multimeric protein composed of 13 subunits of which six possesses two or more isoforms. Selectivity for the osteoclastic V-ATPase could be provided if it has some structural uniqueness, such as a unique isoform combination. The a3 isoform of the 116kDa subunit is inevitable for bone resorption; however, it is also present in, and mainly limited to, the lysosomes of other cells. No evidence of a structural uniqueness of the osteoclastic V-ATPase compared to the lysosomal V-ATPase was found, although this can not yet be excluded. Thus, an inhibitor selective for the a3 isoform would target the lysosomal V-ATPase as well. However, the results suggest that selectivity for bone resorption over lysosomal function can be obtained by two other mechanisms, suggesting that isoform a3 is a valid target. The first is differential compensation; bone resorption depends on the high level of a3 expression, and is not compensated for by other isoforms, while the lower level of a3 in lysosomes of other cells may be partly compensated for. The second mechanism is because the bone resorption process itself is fundamentally different from lysosomal acidification because of the chemistry of bone dissolution and the anatomy of the resorbing osteoclast. By this mechanism, full inhibition of bone resorption is obtained with more than tenfold lower inhibitor concentration than those needed to fully inhibit lysosomal acidification. The two mechanisms are additive. Based on the results, we suggest that bone resorption can be selectively inhibited if VATPase inhibitors that are sufficiently selective for the a3 isoform over the other isoforms are developed.

The Use of Nervous System Drugs and the Risk of Fractures in Old Adults

Hermostoon vaikuttavien lääkkeiden käyttö on yleistä iäkkäässä väestössä. Erityisen yleistä käyttö on pitkäaikaisessa laitoshoidossa asuvilla iäkkäillä. Hermostoon vaikuttavien lääkkeiden haittavaikutuksia on tutkittu paljon, ja useat hermostoon vaikuttavat lääkeaineryhmät on tunnistettu murtumien riskitekijöiksi. Aikaisemmin ei ole kuitenkaan tutkittu usean hermostoon vaikuttavan lääkkeen yhteiskäytön yhteyksiä murtuman riskiin 65 vuotta täyttäneillä. Väitöskirjatutkimuksessa havaittiin, että usean hermostoon vaikuttavan lääkeaineen yhtäaikainen käyttö oli hyvin yleistä Porin kaupunginsairaalan viidellä pitkäaikaisen laitoshoidon osastolla (n = 154) vuosien 2004 ja 2005 vaihteessa. Kolmasosa tutkituista käytti säännöllisesti kolmea tai useampaa hermostoon vaikuttavaa lääkettä samanaikaisesti. Kun huomioitiin myös tarvittaessa otettavat lääkkeet, vastaava luku oli 53 %. Tutkimuksessa havaittiin myös viitteitä lääkkeiden epäasianmukaisesta käytöstä, kun potilaiden käyttämiä lääkkeitä verrattiin heidän kognitiiviseen ja fyysiseen suorituskyynsä sekä asetettuihin diagnooseihin. Liedon kunnassa 1990-luvulla toteutettuun väestöpohjaiseen Liedon Iäkkäät -seurantatutkimukseen osallistui 1177 lietolaista 65 vuotta täyttänyttä. Lääkitystietoja sekä seuranta-aikana tapahtuneita murtumia analysoimalla havaittiin, että kahden tai useamman bentsodiatsepiinin sekä kahden tai useamman psykoosilääkkeen käyttö oli yhteydessä murtuman riskiin 65 vuotta täyttäneillä miehillä. Opioidin ja psykoosilääkkeen yhteiskäyttö sekä opioidin ja bentsodiatsepiinin yhteiskäyttö oli yhteydessä iäkkäiden miesten murtuman riskiin. Naisilla vastaavia tilastollisesti merkitseviä yhteyksiä ei havaittu. Väitöskirjatutkimuksen uusin osa-aineisto perustui Porissa vuosina 2009–2010 toteutetun Satauni-tutkimuksen aineistoon. Tutkimuksessa osoitettiin 89 potilaan aineistossa, että hallittu, yhden kuukauden aikana lääkärin ja hoitajan tuella toteutettu bentsodiatsepiinivieroitus paransi merkitsevästi 55 vuotta täyttäneiden naisten käden puristusvoimaa kuuden kuukauden seuranta-aikana. Vastaavaa yhteyttä ei havaittu miehillä. Bentsodiatsepiinivieroituksella ei ollut yhteyttä osallistujien tasapainotestin tulosten paranemiseen kuuden kuukauden seurantaaikana. Murtumilla on vakavia seurauksia sekä yksilötasolla että yhteiskunnallisesti iäkkäässä väestössä. Murtumien ehkäisy on hyvin tärkeää. Siinä tulee kiinnittää huomiota potilaan käyttämään lääkitykseen ja arvioida erityisesti usean hermostoon vaikuttavan lääkkeen yhteiskäytön tarpeellisuutta.

Primary and Revision Hip Replacement. A University Hospital Database and Registry Study

Large-headed total hip arthroplasty (THA) and hip resurfacing arthroplasty (HRA) with metal-on-metal (MoM) bearings became popular during the last decade. Recently, it has become evident that the large-head MoM hip implants are associated with increased revision rates despite their theoretical advantages. The purpose of this study was to evaluate the early results of primary MoM hip replacements and of acetabular revisions. I analyzed retrospectively the results of four MoM implant designs and the survival rate of acetabular revisions with impaction bone grafting, as documented in the Turku University Hospital database. Further, I evaluated the correlation between femoral head size and dislocation rate, and used the Finnish Arthroplasty Register data to compare the survival of three large-head MoM THAs to analogous HRAs. The early results for the Magnum M2A–ReCap THA were good. A larger head size decreased the risk of dislocation. Articular surface replacement (ASR) THA yielded inferior results compared to analogous HRA. For two other designs the results were similar. The R3–Synergy THA yielded inferior results compared to the reference implants. The survival of acetabular reconstructions with impaction bone grafting was inferior compared to previous reports. In conclusion, the early results of the Biomet ReCap–Magnum design were promising, and large head sizes decreased the dislocation rate. The survival of different MoM hip implant designs varied. The survival of new designs and techniques may be inferior to those reported by the clinics where implants are developed. An important caveat is that early promising results of new devices may rapidly worsen. New implants need to be introduced in a controlled fashion to the market; here, arthroplasty registers are a valuable tool that needs to be used.