CME*--...

SUMMARYFracture of an ankylosed spineis often overlooked. Because theforce that damages anankylosed spine is frequentlyslight, patients do not realizethey are injured. Doctors canmiss the fracture for the somereason and because patientsalready have a history of hackpain. Plain radiographssometimes fail to demonstratethe fracture site.

RESUMEChez le patient atteintd'ankylose de la colonne,la fracture d'une vertebre passesouvent inapercue. Puisqu'untraumatisme mineur peutfrequemment causer desdommages a une colonneankylosee, les patients nerealisent pas l'importancede leur blessure. Pour la memeraison, les medecins peuventmanquer la fracture d'outantplus que ces patients ont dejades antecedents de douleursa la colonne. Les radiographiessimples sont parfois incapablesde mettre en evidence le site dela fracture.Can Fam Physicion 1995;41:1213-1216.

Ankylosed spines

are prone to fracture

THOMAS HUNTER, MB, FRCPCBRUCE FORSTER, MD, FRCPCMARCEL DVORAK, MD, FRCSC

HE ANKYLOSED SPINE IS MORE

prone to fracture thannormal spines. This phe-nomenon has been report-

ed in both ankylosing spondylitisand diffuse idiopathic skeletalhyperostosis.1-7 Fractures are morecommon in patients with ankylosingspondylitis because of associatedspinal osteoporosis.'The force causing fracture of the

ankylosed spine is often minor, andpatients might be unaware that it seri-ously damaged the spine. If patientsdo visit physicians, the complicationof spinal fracture could be overlookedbecause of the minor nature of thetrauma and the patients' history ofspinal pain. If the diagnosis is consid-ered, plain radiographs of the spinemight fail to demonstrate the fracturesite."2 The following case report illus-trates these problems.

Dr Hunter is Clinical Professor ofMedicineat the University ofBritish Columbia (UBC) inVancouver, and a member ofthe Division ofRheumatology, Dr Forster is ClinicalAssistant Professor ofRadiology at UBC and isa member ofthe Department ofRadiology,Dr Dvorak is Clinical Instructor ofOrthopedics at UBC and is a member oftheDepartment of Orthopedics, all at the VancouverHospital and Health SciencesCentre.

Case reportA 43-year-old man with a 20-year his-tory of ankylosing spondylitis hadradiographic evidence of ankylosis ofthe entire spine. He slipped and fell inhis kitchen; the next morning, he hadno pain at rest, but on movement hehad midthoracic pain. He wasbrought to the emergency departmentby ambulance and handled as if hehad a spinal fracture. Examinationshowed no tenderness of the spine,and results of the neurological exami-nation were normal.

Plain radiographs of the thoracicspine showed no definite abnormality(Figure 1). However, a radionuclidebone scan showed increased radionu-clide uptake at the T8-9 level(Figure 2). Tomography at the T8-9level demonstrated a fracture(Figure 3). Radiographs of the cervicalspine, when compared with radi-ographs done 6 months previously,showed a fracture through the ossifiedanterior longitudinal ligament at theC5-6 level (Figure 4). No correspond-ing abnormality was seen on theradionuclide bone scan. The patientwas treated conservatively for spinalfractures of the cervical and thoracicregion, and at a 6-month follow-upexamination, the fractures had healedwith no neurological complication.

Canadian Famiy Physician VOL 41:JU1y 1995 1213

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Figre 2. Radinide bone sca sowing

increased uptake ofradionuclideat -the T8-9lelvel

F.iure 3. of the. horacic spineshowing a frcture at the TB-9 level

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1214 Canadian Family Physician VOL 41:JUly 1995

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DiscussionThis case illustrates many of the clini-cal features associated with spinalfractures in patients with ankylosingspondylitis. First, most patients have ahistory of chronic spinal pain fol-lowed by a pain-free period once thebony ankylosis has occurred. Theredevelopment of mechanical spinalpain, precipitated or aggravated byactivity and relieved by rest, shouldsuggest a spinal fracture. In addition,patients might notice a change in pos-ture or a change in their field of view.The fracture might occur at morethan one level. If the fracture occursin the thoracic region, patients mustbe watched closely, as laceration ofthe aorta could occur.8'9The fracture might be difficult to

see on plain radiographs, especiallyat the cervicothoracic junction,which could be the most commonsite of fracture in patients with anky-losing spondylitis."2 Therefore, if thediagnosis is considered, patientsshould be managed as if they have aspinal fracture until other studies canbe completed.

Radionuclide bone scanning is nowavailable in many smaller hospitals andcould help to locate the spinal fracture,which can then be confirmed by radi-ographic tomography (Table 1).2Computed tomography (CT) is

becoming increasingly available. As thefracture is often in the transverse planeand undisplaced, CT performed axial-ly might miss the fracture dependingon the slice thickness. Reformating thedata into the sagittal plane might makesuch a fracture apparent.10"l However,plain film tomography, if available,might be just as useful.

Magnetic resonance imaging can alsodetect a radiographically occult spinalfracture, because of the associated bonemarrow edema." The fracture itself,however, is probably more visible withCT or tomography. Magnetic resonanceimaging might also be helpful in diagnos-ing an epidural hematoma, which ismore common in spinal fractures inpatients with ankylosing spondylitis.'2 U

Correspondence to: Dr Thomas Hunter,Division of Rheumatology, Vancouver Hospital,855 West 12th Ave, Vancouver, BC V5Z 1M9

References1. Hunter T, Dubo H. Spinal fractures compli-cating ankylosing spondylitis. Ann Intern Med1978;88:546-9.

2. Hunter T, Dubo HIC. Spinal fracturescomplicating ankylosing spondylitis. Alongterm follow-up study. Arthritis Rheum1983;26:751-9.

3. Hunter T. The spinal complications of anky-losing spondylitis. Sernin Arthritis Rfheum 1989;19:172-82.

4. Fardon DE Odontoid fracture complicatingankylosing hyperostosis of the spine. Spine1978;3: 108-12.

5. Houk RW, Hendrix RW, Lee C, Lal S,Schmid FR. Cervical fracture and paraplegiacomplicating diffuse idiopathic skeletal hyper-ostosis. Arthritis Rheum 1984;27:472-5.

6. Corke CE Spinal fracture and paraplegiaafter minimal trauma in a patient with anky-losing vertebral hyperostosis. BMJ 198 1;282:2035.

Continued on page 1216

Table 1. How to diagnose a fracture in an ankylosed spine

Step 1. Suspect the diagnosis if there are:

* a history of direct or indirect trauma to the spine of even a mild degree(usually a simple fall),

* complaints ofmechanical spinal pain precipitated or aggravated byactivity and completely or partially relieved by rest, or

* a change in posture, including improved posture.

.....................................................................................................................................................

Step 2. Once the diagnosis is suspected, manage the patient as having anunstable spinal fracture until the diagnosis has been excluded. (Suspect thatthere might be more than one fracture site.)

Step 3. Perform radiographic examination of the spine.

Step 4. If the radiographs suggest a spinal fracture, confirm with computedtomography.

Step 5. If findings from radiographs are negative and if it is unclear whichareas should be submitted to tomography, then a bone scan might help identifythe fracture site.

CME

Ankylosed spinesare prone to fracture

Canadian Family Physician VOL41:jUy 1995 1215

7UCUR(simvastatin tablets)

Tablets 5, 10 and 20 mgCholesterol-lowering agentINDICATIONS AND CLINICAL USEAs an adjunct to diet for the reduction of elevated total and LDL-C levels inpatients with primary hypercholesterolemia; also in combined hypercholes-terolemia and hypertriglyceridemia, when hypercholesterolemia is theabnormality of most concern.To determine which patients to treat, initially establish that the elevation inplasma lipids is not due to underlying conditions such as poorly-controlleddiabetes mellitus, hypothyroidism, the nephrotic syndrome, liver disease, ordysproteinemias. Then ascertain whether elevated LDL-C level is the cause forelevated total serum cholesterol, particularly in patients with total triglyceridesover 4.52 mmol/L (400 mg/dL) or with markedly elevated HDL-Cvalues, where non-LDL lipoprotein fractions may contribute significantly tototal cholesterol levels, without apparent increase in cardiovascular risk.CONTRAINDICATIONSHypersensitivity to any component. Active liver disease or unexplainedDersistent elevations of serum transaminases. Pregnancy and lactation (seePRCAUTIONS).WARNINGSThe effects of simvastatin-induced changes In lipoprotein levels,Including reduction of serum cholesterol, on cardiovascularmorbidity or mortality have not been established.1. Hepatic effects: In clinical trials, marked persistent increasesIn serum transaminases occurred in 1% of adult patients whoreceived simvastatin (see ADVERSE REACTIONS). Increases were notassociated with jaundice or other clinical signs or symptoms. There was noevidence of hypersensitivity. Serum transaminases fell slowly to pre-treatmentlevels when drug was interrupted or discontinued.All patients should have liver function tests at baseline andperiodically thereafter. Patients who develop elevated serumtransaminase levels require special attention, prompt retesting and morefrequent testing.Discontinue drug if transaminase levels show evidence ofprogression, particularly a rise to 3 times the upper limit ofnormal that persists.Use with caution in patients who consume substantial quantities of alcoholand/or have a history of liver disease. Discontinue drug if active liver diseaseor unexolained persistent transaminase elevations develop during therapy (seeCONTRAINDICATIONS).Moderate elevations of serum transaminases, reported with simvastatin, havealso been observed with other, comparative lipid-lowering agents. Thesechanges generally appeared within the first 3 months after initiation of therapy,were often transient, not accompanied by any symptom, and did not needinterruption of treatment.2. Muscle Effects - CPK: Transient elevation of creatine phosphokinase(CPK) levels commonly seen, usually have no clinical significance. -Myalgia and muscle cramps have also been observed. - Myopathy reportedrarely (0.05%); consider possibility in any patient with diffuse myalgias,muscle tenderness and/or marked elevation of creatine phosphokinase(. 10 times the upper limit of normal). Ask patients to promptly reportunexplained muscle pain, tenderness and weakness. With lovastatin, a closelyrelated HMG-CoA reductase inhibitor, the risk of myopathy is known to besubstantially increased by concomitant immunosuppressive drugs includingcyclosporins, or gemfibrozil or lipid-lowering doses of niacin. Severe rhabdo-myolysis that precipitated acute renal failure was reported. Also, rhabdo-myolysis with or without renal impairment was reported in seriously illpatients receiving concomitant erythromycin and lovastatin.Therefore, carefully consider benefits and risks of concomitant use ofsimvastatin with immunosuppressive drugs, fibrates, erythromycin or lipid-lowering doses of niacin. Consider interrupting simvastatin in any patient withan acute, serious condition, suggestive of a myopathy or a risk factorpredisposing to development of renal failure or rhabdomyolysis, such as:severe acute infection, hypotension, major surgery, trauma, severe metabolic,endocrine or electrolyte disorders and uncontrolled seizures.PRECAUTIONSGeneral: Before starting therapy, attempt to control hypercholesterolemiawith appropriate diet, exercise, weight reduction in overweight and obesepatients, and to treat underlying medical problems (see INDICATIONS). Thepatient should inform subsequent physicians of prior use of simvastatin.Ophthalmic evaluations: Current data do not indicate adverse effects onthe human lens, but long-term effects have not been established. Periodicophthalmological exams are recommended, keeping in mind that even withoutdrugs, an increased prevalence in lens opacities could be expected withaging. Use in homozygous familial hypercholesterolemia:simvastatin is unlikely to be of clinical benefit. Effect on Lipoprotein(a)[Lp(a)]: In some patients, the beneficial lowering of total and LDL cholesterolmay be partly blunted by increased Lp(a) levels. Pending further experience,Lp(a) plasma levels should be measured when feasible in patients givensimvastatin. Hypersensitivity: A few instances of eosinophilia and skineruptions appear to be associated with simvastatin. If hypersensitivitysuspected, discontinue drug. Carcinogenesis: In animal studies, increasedincidences of hepatocellular adenomas and carcinomas, pulmonary adenomasand harderian gland adenomas were noticed in mice receiving 500 times themaximum recommended human dose. Female rats receiving 31 times themaximum recommended human dose exhibited an increased incidence ofthyroid follicular adenomas. (See TOXICOLOGY Section of ProductMonograph.)Use in obstetrics: Simvastatin is contraindicated during pregnancyand there are no data on such use. Because the HMG-CoA reductaseinhibitors are able to decrease the synthesis of cholesterol and possibly otherproducts of the cholesterol biosynthesis pathway that are essentialcomponents for fetal development, simvastatin may cause fetal harm.Administer to women of childbearing age only when they are highly unlikelyto conceive. It a patient becomes pregnant, apprise her of potential hazard Inthe fetus, and discontinue drug. Nursingl mothers: Whether simvastatin isexcreted in human milk is unknown. However, because of the potential forserious adverse reactions, women taking simvastatin should not nurse (seeCDNTRAINDICATIDNS). Pediatric use: Safety and effectiveness have notbeen established; therefore simvastatin therapy in children is not yetrecommended. Use in patients with impaired renal function: Exercisecaution if renal function impairment is significant.

3® Trademark Merck & Co., Inc./Merck Frnsst Canada Inc., R.U.

Drug InteractionsConcomitant therapy with other lipid-lowering agents: Cholesterol-lowering effects of simvastatin and cholestyramine appear additive. Exercisecaution when coadministering with other lipid-lowering agents, particularlygemfibrozil and niacin (see WARNINGS). Erythromycin: See WARNINGS:Muscle effects. ACE Inhibitors: Hyperkalemia associated with myositis wasreported in a single patient with insuain-dependent diabetes mellitus and mildrenal insufficiency who received another HMG-CoA reductase inhibitor:lovastatin with an ACE inhibitor, lisinopril. Coumarin anticoagulants:Determine prothrombin time in patients on concomitant coumarin anti-coagulants before starting simvastatin therapy and monitor periodically,because anticoagulant effect of warfarin appeared to be slightly enhanced bysimvastatin use. Digoxin: Digoxin plasma concentrations were slightlyelevated by coadministration of simvastatin. Propranolol: No clinicallysignificant pharmacokinetic or pharmacodynamic interaction noted withconcomitant simvastatin. Antipyrine: Simvastatin had liffle or no effect onthe pharmacokinetics of antipyrine. Other concomitant therapy: Exercisecaution with coadministration of immunosuppressants (see WARNINGS). Inclinical studies, simvastatin was used with beta-blockers, calcium-channelblockers, diuretics and NSAIDs, without evidence of clinically significantadverse interactions.Drug/laboratory test interactions: Simvastatin may elevate serumtransaminase and creatine phosphokinase levels (see ADVERSE REACTIONS).In differential diagnosis of chest pain in patients on simvastatin, determinecardiac and non-cardiac fractions of these enzymes.ADVERSE REACTIONSSimvastatin was found generally well tolerated, and adverse reactions usuallymild and transient, based on experience in over 2300 patients, of whom over1200 were treated for 1 year and over 230 for 2 years or more. In controlledclinical trials, 1% were withdrawn due to adverse experiences affributable tosimvastatin. Adverse experiences occurring at an incidence of .0.5% of 2361patients treated with simvastatin in controlled clinical studies and reported tobe possibly, probably or definitely drug related are shown in the table below:

ZOCOR®(n=2361)%

GastrointestinalAcid Regurgitation 0.5Constipation 2.5Dyspepsia 0.6Diarrhea 0.8Flatulence 2.0Nausea 1.1

Nervous SystemHeadache 1.0

SkinRash 0.7

MiscellaneousAbdominal Pain 2.2Asthenia 0.8

Ophthalmological Observations: see PRECAUTIONS.Laboratory tests: Marked persistent increases of serum transaminasesnoted (see WARNINGS). About 5% of patients had elevations of CPK levelsof at least three times normal value, affributable to the non-cardiac fractionof CPK, on one or more occasions. Myopathy reported rarely (seeWARNINGS and PRECAUTIONS).Others: Though not observed in clinical trials with simvastatin, the followinghave been reported with other HMG-CoA reductase inhibitors: hepatitis,cholestatic jaundice, vomiting, anorexia, paresthesia, psychic disturbancesincluding anxiety, and hypospermia. Also reported rarely with lovastatin was ahypersensitivity syndrome which included one or more of the following:anaphylaxis, angioedema, lupus-like syndrome, polymyalgia rheumatica,thrombocytopenia, leukopenia, hemolytic anemia, positive ANA, ESR increase,arthritis, arthralgia, urticaria, asthenia, photosensitivity, fever and malaise.SYMPTOMS AND TREATMENT OF OVERDOSAGENo experience of deliberate or accidental overdosage. Treatment should besymptomatic and supportive, liver function should be monitored, andappropriate therapy instituted. Dialyzability of simvastatin not known.DOSAGE AND ADMINISTRATIONBefore initiating simvastatin, place patient on standard cholesterol-loweringdiet, and continue on this diet during treatment. If appropriate, implement aprogram of weight control and exercise. Usual starting dose: 10 mg/day, asa single dose in the evening. Make dosage adjustments, if necessary, atintervals of not less than 4 weeks, to maximum of 40 mg daily, given as asingle evening dose. Monitor cholesterol levels periodically andconsider reducing dosage if cholesterol levels fall below targetedrange, as recommended by the Canadian Consensus Conferenceon Cholesterel.Concomitant therapy: Cholesterol-lowering effects of simvastatin andcholestyramine a ear additive. For use with other lipid-lowering agents, seeWARNINGS and ECAUTIONS.AVAILABILITY AND DOSAGE FORMSZOCOR® Tablets are shield-shaped, film-coated, engraved with a code on oneside and Z on the other. ZOCOR® 5 mg and 10 mg tablets are available inblister packs of 30 tablets. 10 mg tablets available in boufles of 500s. 20 mgtablets available in boftles of 100s.- ZOCOR 5 mg, buff tablet, engraved 726.- ZOCOR® 10 mg, peach tablet, engraved 735.- ZOCOR®t20 mg, tan tablet, engraved 740.PRODUCT MONOGRAPH AVAILABLE ON REQUEST(508x-a,7,94)Reterences:1. The Scandinavian Simvastatin Survival Study Group. Randomized trial of

cholesterol lowering in 4444 patients with coronary heart disease: theScandinavian Simvastatin Survival Study (4S). Lancet 1994;344:1383-89.

8526,8582, 8592

MEMBER

PM | PAAB |

o MERCK FROST

FROSSTDIV. OF MERCK FROSST CANADA INC.P.O. BOX 1005, POINTE-CLAIREDORVAL, QUEBEC H9R 4P8

CME*---00

7. Mody GM, Charles RW, Ranchod HA,Rubin DL. Cervical spine fracture indiffuse idiopathic skeletal hyperostosis.J Rheumatol 1988; 15:129-31.

8. Fazl M, BilbaoJM, Hudson AR.Laceration of the aorta complicatingspinal fracture in ankylosing spondylitis.Neurosurgery 1981 ;8:732-4.

9. Schaberg FJ. Aortic injury occuring afterminor trauma in ankylosing spondylitis.7 Vasc Surg 1986;4:410- 1.

10. Fishman EK, Magid D. Cervical frac-ture in ankylosing spondylitis: value ofmultidimensional imaging. Clin Imaging1992; 16:31-3.

11. Goldberg AL, Daffner RH,Schapiro RL. Imaging of acute spinaltrauma: an evolving multi-modalityapproach. Clin Imaging 1990; 14:11-6.

12. Farhat SM, Schneider RC, GrayJM.Traumatic spinal extradural hematomaassociated with cervical fracture inrheumatoid spondylitis. 5 Trauma 1973;13:591-8.

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1216 Canadian Family Physician VOL 41: Jul 1995