stephanie kimbrel diane morris heather sloan. osteitis deformans second most common bone disease...

39
Paget Disease Stephanie Kimbrel Diane Morris Heather Sloan

Upload: colleen-madlyn-jefferson

Post on 18-Jan-2016

218 views

Category:

Documents


0 download

TRANSCRIPT

Pagets Disease

Paget DiseaseStephanie KimbrelDiane MorrisHeather Sloan

Sir James Paget

Diagnosed disease in 1877, also the founder father of pathology2Paget Disease Osteitis Deformans Second most common bone disease after osteoporosis

3Bones Most Commonly Involved PelvisFemurTibiaSpineSkull

EpidemiologyViral: Measles Respiratory Syncytial Virus (RSV) Slow Virus (paramyxoviruses): present for years before symptoms appear

Examples of paramyxoviruses are RSV, influenza and measles5EpidemiologyGenetic 15% to 40% of persons with the disease have a first-degree relative with the disease, numerous studies also show other relatives with the disease Sequestrosomel 1(one) gene on chromosome 5

Demographics/Cultural ConsiderationsFirst appeared in Western Europe populations with the earliest documented cases dating back to the Roman and Anglo-Saxon periods in EnglandClosely parallels patterns of migration from Western Europe

Demographics/Cultural ConsiderationsPatients with a family history are more likely to have parents born in Europe than those with sporadic diseaseNew England has the highest number of patients with the diseaseDemographics/Cultural ConsiderationsDisease is uncommon before the age of 40By the age of 80, 1 out of 10 persons is affected18% to 25% of the US population have one family member with Paget DiseasePaget Disease: DefinitionPagets disease of the bone is a focal disorder of chaotic bone remodeling with increased osteoblastic and osteoclastic activity that results in disorganized woven and lamellar bone in one or more skeletal sites.

End result is bone of poor quality that is enlarged, hypervascular, and susceptible to deformation and fracture

Anatomy and PhysiologyOSTEOBLASTSOSTEOCLASTS*Functions in building *Functions in the the osseous matrix of breakdown of the bone the bone matrix

Maintenance of normal bone function depends on two types of cells:

11Anatomy and Physiology

Bone remodelingInvolves an orderly sequence of osteoclastic bone reabsorption, the formation of new bone by the osteoblasts, and mineralization of the newly formed osteoid tissue.

12PathophysiologyIncreased osteoclastic numbersOsteoclastic are abnormal in size and activity with excessive nuclei.Leads to voids and cavities in the boneFollowed by chaotic bone formation by osteoblasts.New bone is woven vs. lamellarCollage of mosaic matrixHypervascularity

Metabolic hyperactivity of the bone surfaceOsteoblasts fill in the voids and cavitiesWoven vs. Lamellar: structurally less competent and occupies more spaceThe irregular cement lines give rise to a mosaic patchwork appearance at the bones histologic exam

13PathophysiologyMineralization rates are normalBone remodeling normally: 10-15% of bone surfaces May increase five to ten fold.Cortex= increases its porosity and blurs the distinction between cortical and cancellous boneNewly formed bone is not organized and irregularBone enlargementDeformity

But because abnormally large volumes of bone are undergoing mineralization, the surface covered with unmineralized osteoid is increased.Bones are less resistant and more elastic=deformity and fracturesBone enlargement: Limbs, skull, facial bones= neurological sxDeformity: bowing in the long bones

14Three Phases: Phase OneInitial short lived burst of multinucleate osteoclastic activity causing bone resoprtionDuring this phase there is a marked elevation of serum alkaline phosphate (SAP)Early Lytic phase or hot phasePaget disease rarely is diagnosed in the initial lytic phase. At this early point of the disease, osteoclastic activity is predominant. Paget disease usually begins at the end of a bone, except when it occurs in the tibia. A characteristic sharply demarcated zone of osteolysis may begin in the subcortical bone and advance along the diaphysis. Osteoblastic activity lags behind; thus, radiolucent fibrous tissue replaces normal bone.15Phase TwoA mixed phase of both osteoclastic and osteoblastic activity with increased levels of bone turnover leading to deposition of structurally abnormal boneExcessive activity=deformitiesThe intermediate or mixed phase reveals evidence of osteolytic and disorganized osteoblastic activity. New bone forms abnormally and demonstrates characteristically coarsened trabecula and cortical thickening in the cancellous and compact bone, respectively. Characteristic intracytoplasmic inclusions may be observed microscopically, supporting evidence for the viral etiology theory.16Phase ThreeFinal chronic sclerotic phase during which the bone formation outweighs bone resportionCombined with old age leads to arthritisCan lead to chronic non-specific inflammation and occasional narrowing of the foramensThe final or cold phase demonstrates less evidence of continual osseous remodeling. Previously laid down woven bone is converted to dense lamellar bone. Histologic features of disorganized bone are prominent. The intersecting lines of remodeled bone have a characteristic mosaic pattern histologically.17

On the right, an X-ray of an upper arm bone (humerus) shows the abnormal growth associated with Paget's disease. The same person's other, normal humerus is shown in the X-ray on the left.18

Whole-body bone scan in a patient with polyostotic Paget disease reveals intense uptake of radiopharmaceutical in the femur, pelvis, spine, and proximal right humerus. The cortical discontinuity of the proximal right humerus represents an insufficiency fracture (arrow). Courtesy of Lee F. Rogers. 19

Disease of the spinePelvis thick, wide and patchy (Cotton wool patches.)20Differential DiagnosisOsteoarthritisGoutPseudogoutOsteomalacia

Osteoarthritis A degenerative joint disorderResult of mechanical and biologic events that destabilize the normal process of degradation and synthesis of articular cartilage chondrocytes, extracellular matrix, and subchondral bone

Prevalence increases with ageInvolves the entire jointMost commonly affected joints are the hands, knee, hip, hands, and lumbar & cervical spinePresents with joint pain and stiffness: worse with activityBone resorption > bone formationLocations include the spine, hip and kneeDifferential: is osteoarthritis involves the handsnormal lab valuesOften referred to as the wear and tear arthritisSlowly destructive disorder of the articular cartilageCan present as primary disease of unknown etiology or secondary disorder related to congenital or acquired defects that affect joint distress

22Key diagnostic criteriaX-rays reveal new bone formation, joint space narrowing, and subchondral sclerosis and cysts

Pain associated with activities, weight-bearing joints being associated with weight-bearing activitiesPain at rest or at night is unusual (except with advanced OA)Functional difficultiesCommonly involved joint HANDS, knee, hip, and lumbar & cervical spineBouchard nodes (PIP) and Heberden nodes (DIP)Limited ROM, both limited and activeBony malalignment

Hand OA spared MCP joint

23GoutA syndrome characterized by:HyperuricemiaDeposition of urate crystals causing attacks of acute inflammatory arthritisTophi around the jointsAnd possible joint destruction

Metabolism and elimination of uric acidCrystal deposition produces arthritisRecurrent attacks, normally in men with peak incidence in the fourth to sixth decadeMonoarticular affecting tarsal joints, ankles, heels, knees, wrists, fingers and elbowsIncreased Uric AcidRapid onset of pain, swelling, erythema of distal joint and/or periarticular soft tissueSynovial aspirate=dx24Key diagnostic criteriaArthrocentesis with synovial fluid analysisUric acid level: men >7mg/dL, women >6mg/dLX-ray reveals periarticular erosions (overhanging edge or punched-out appearanceMen aged 40-60 yearsUse of gout-inducing medicationConsumption of meat, seafood, or alcohol Rapid-onset of severe painJoint stiffnessFew affected jointsSwelling and joint effusionTendernessTophiFoot joint distributionErythema and warmthFamily hx

PseudogoutAcute synovitis caused by calcium pyrophosphate dihydrate crystals.

Acute Attack:Monoarticular attacks: knee

Joint inflammation, pain, heat, redness of the swelling, and chillsProximal muscle painCLINICAL PRESENTATIONPart of the tissue aging processCartilage degeneration and the shedding of calcium pyrophosphate crystals into joint cavity= painChronic inflammationCan also present with proximal muscle pain

26Key diagnostic criteriaArthrocentesis with presence of weakly positive birefringent rhomboid shaped crystals. ( yellow perpendicular and blue parallel to polarizer axis)Synovial fluid should be analyzed.Plain radiographs often reveal chondrocalcinosis located parallel to subchondral bone: knee menisci, wrist triangular fibrocartilage and symphisis pubisGenerally affects older people and both men and women equally

OsteomalaciaA metabolic bone disease characterized by incomplete mineralization of the underlying mature organic bone matrix following growth plate closure in adults. Rickets is a different manifestation of the same underlying pathologic process.(Buttaro, T.M., Trybulski, J., Bailey, P.P., Sandberg-Cook, J. , 2008; Holick, M.F. , 2007)

Key diagnostic criteriaPrimarily vitamin D deficiency. No differentiating s/s yet osteomalacia is more likely to present with s/s of bony tenderness and pain. Diagnostics- Elevated serum 25 hydroxyvitamin D levels (normal in Paget disease)Elevated total serum alkaline phosphatase level (normally markedly elevated in Paget disease)Normal serum calcium in Paget diseaseX-ray shows gross deformities of bone such as enlargement of the skull in Paget disease

(Holick, M.F. , 2007; Van Staa, T.P., Selby, P., Leufkens, H.G., et al. , 2002; Whitehouse, R.W. ,2002)

When to treat?Extensive or symptomatic disease; neurological complications; serum alkaline phosphatase level 3-4 times normal; weight bearing bones, skull, or vertebrae involvement.Goal is to prevent progression by suppressing osteoclastic activity which allows the osteoblasts to catch up and lay normal bone(Buttaro, T.M., Trybulski, J., Bailey, P.P., Sandberg-Cook, J., 2008; Ferri, F., 2012)

Treatment options1.) Calcium and vitamin D 2.) Oral Bisphosphonates (alendronate [Fosamax], risedronate [Actonel])3.) IV Bisphosphonates ( pamidronate [Aredia], zoledronic acid [Zometa])4.) Calcitonin5.) Pain management- Acetaminophen, ASA, NSAIDS(Buttaro, T.M., Trybulski, J., Bailey, P.P., Sandberg-Cook, J., 2008; Ferri, F., 2012)

Follow upDisease activity is monitored by biochemical markers (SAP or NTx) measured q 3-6 months in active disease or yearly in inactive diseaseAssess pain, joint symptoms, neurologic function, and medication side effects every visit. Refer to orthopedics/neurosurgery when an arthropathy or spinal stenosis causes unremitting pain or function loss.(Buttaro, T.M., Trybulski, J., Bailey, P.P., Sandberg-Cook, J., 2008; Ferri, F., 2012)

Pagets Disease at a GlancePaget's disease is a chronic bone disorder.Paget's disease frequently causes no symptoms.Paget's disease can cause pain in the bones or joints, headaches and hearing loss, pressure on nerves, increased head size, bowing of limb, or curvature of spine.Tests used to diagnose Paget's disease include X-rays, blood tests, and bone scanning.Paget's disease can lead to other medical conditions.Medical treatment options include aspirin, other anti-inflammatory medications, pain medications, and medications that slow the rate of bone turnover, decreasing the activity of Paget's disease.Surgical operations may necessary for damaged joints, fractures, severely deformed bones, or when nerves are being pinched by enlarged bone.

QuestionWhich bones are most commonly involved in Pagets Disease? a) Skull b) Spine c) Tibia d) Femur e) Pelvis f) All of the aboveQuestionWhat does the word osteoblasts mean? a) Functions in the building of the osseous matrix of the bone b) Functions in the breaking down of the bone c) NeitherQuestionWhat lab is elevated when trying to rule out a diagnosis for Pagets Disease? a) Uric Acid b) Serum Alkaline Phosphate (SAP) c) Hydroxyvitamin D levelReferencesAnsiello & Goldman (2004). Cicil Textbook of Medicine (22nd ed.). Philidelphia, PA: SaundersButtaro, T.M., Trybulski, J., Bailey, P.P., Sandberg-Cook, J. (2008). Primary Care: A Collaborative Practive (3rd ed.). St. Louis, MO: MosbyFerri, F. (2012). Ferris Clinical Advisor. Providence, Rhode Island: Mosby.Holick, M.F. (2007). Vitamin D Deficiency. New England Journal of Medicine, 357, 266-281Matfin, G., Mattson Porth, C., (2009). Pathophysiology-Concepts of Altered Health States (8th ed.). Philadelphia, PA: Wolters Kluwer & Lippincott Williams & Wilkins.Thompson, J.C. (2010). Netters Concise Orthopaedic Anatomy (2nd ed.). Philidelphia, PA: SaundersVan Staa, T.P., Selby, P., Leuflkens, H.G., et al. (2002). Incidence and Natural History of Pagets Disease of Bone in England and Wales. Bone Miner, 17, 465-471.Whitehouse, R.W. (2002). Pagets Disease of Bone. Semin Musculoskeletal Radiol, 6, 313-322

Photography Referenceshttp://emedicine.medscape.com/article/394165-overview#a01http://www.google.com/search?q=pictures+of+osteoclast&hl=en&qscrl=1&nord=1&rlz=1T4ADRA_enUS432US433&prmd=imvns&tbm=isch&tbo=u&source=univ&sa=X&ei=4y1YT5ynHs3DsQLL48WvDQ&ved=0CCIQsAQ&biw=1366&bih=627http://www.google.com/search?q=pictures+of+osteoblasts&hl=en&qscrl=1&nord=1&rlz=1T4ADRA_enUS432US433&prmd=imvns&tbm=isch&tbo=u&source=univ&sa=X&ei=5kVYT529AuOssQKU_endDQ&ved=0CC8QsAQ&biw=1366&bih=627http://www.mayoclinic.com/health/pagets-disease-of-bone/DS00485http://en.wikipedia.org/wiki/Paget's_disease_of_bonehttp://osteoarthritis.about.com/od/osteoarthritis101/ss/explained_8.htmhttp://www.gout-aware.com/gout-and-pseudogout.html