presentation by: dr. louis ricca clinical associate professor of medicine university of south...
TRANSCRIPT
![Page 1: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/1.jpg)
Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida
Diagnosis and Management of Paget’s Disease of Bone
Sir James Paget1814-1899
![Page 2: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/2.jpg)
History of Paget’s Disease
• Sir James Paget named disease osteitis deformans in 1876, suspecting basic inflammatory process1,2
• Today predominantly referred to as Paget’s disease of bone1
![Page 3: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/3.jpg)
![Page 4: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/4.jpg)
What is Paget’s Disease?
![Page 5: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/5.jpg)
![Page 6: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/6.jpg)
![Page 7: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/7.jpg)
Paget’s Disease: Description
• Chronic, progressive skeletal disorder
• Increased size and number of osteoclasts
• Localized areas of excessive bone resorption and formation– May have only one affected bone or have
pagetic lesions in multiple bones
– New lesions rarely develop in previously unaffected bone after diagnosis
![Page 8: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/8.jpg)
Epidemiology: Prevalence of Paget’s Disease in the US
1. Siris ES, Roodman GD. In: Favus MJ, ed. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. 6th ed. Washington, DC: ASBMR; 2006:320-330. 2. Altman RD, et al. J Bone Miner Res. 2000;15:461-465.
• Second most common bone disease after osteoporosis1
• Roughly estimated at approximately 2% of the US population over age 55 years1
– Prevalence increases markedly with age, uncommon before age 401,2
• 15% to 30% of patients have positive family histories1
• Most common in people of Northern European descent1
![Page 9: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/9.jpg)
![Page 10: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/10.jpg)
![Page 11: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/11.jpg)
![Page 12: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/12.jpg)
Histology of Pagetic Bone
Paget’s Disease: An Osteoclast-Mediated Disorder
Osteoclasts
Multinucleated osteoclast
Courtesy of Pierre Delmas, MD.
Multinucleatedosteoclast
![Page 13: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/13.jpg)
![Page 14: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/14.jpg)
![Page 15: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/15.jpg)
![Page 16: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/16.jpg)
Siris ES, Roodman GD. In: Favus MJ, ed. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. 6th ed. Washington, DC: ASBMR; 2006:320-330.
Pagetic Bone and Normal Bone
Normal Pagetic
![Page 17: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/17.jpg)
Osteoclast Nucleus Osteoclast Nucleus Containing Measles-like Containing Measles-like Nucleocapsid StructureNucleocapsid Structure
X 32,000X 32,000
![Page 18: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/18.jpg)
Paget’s Disease: Clinical Presentation
• Usually mild or asymptomatic1
• Diagnosis is often based on incidental findings1
– Elevated total or bone specific serum alkaline phosphatase
– Radiological findings • Patients may present with symptoms that are nonspecific
or suggestive of other conditions1
– Pain– Fracture– Deformity– Osteoarthritis– Hearing loss
1Siris ES, Roodman GD. In: Favus MJ, ed. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. 6th ed. Washington, DC: ASBMR; 2006:320-330.
![Page 19: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/19.jpg)
Paget’s Disease: Common Sites of Involvement
• Paget’s disease can occur in any bone, but most commonly:
– Skull
– Vertebrae
– Pelvis
– Femur
– Tibia
![Page 20: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/20.jpg)
Diagnosing Paget’s Disease: Tests
• Laboratory tests1,2
– Alkaline phosphatase, a marker of bone formation
– Any level above normal, especially in the absence of elevated liver enzymes– Bone-specific alkaline phosphatase may be more
reliable. Elevated markers of bone resorption (serum βC-telopeptide of type 1 collagen [CTX], urine N-telopeptide of type I collagen [NTX])
• Radiographs1,2
– Characteristic appearance usually confirms diagnosis
• Bone scan to assess extent of disease1
1. Lyles KW, et al. J Bone Miner Res. 2001;16:1379-1387. 2. Selby PL, et al. Bone. 2002;31:366-373.
![Page 21: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/21.jpg)
![Page 22: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/22.jpg)
Complications of Paget’s Disease: Neurologic Disorders
• Hearing deficit• Cranial nerve deficits• Mottled retinal degeneration;angioid streaks• Basilar impression• Hydrocephalus• Myelopathy• Radicular neuropathies• Spinal stenosis• Spinal vascular steal syndrome
![Page 23: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/23.jpg)
Lyles KW, et al. J Bone Miner Res. 2001;16:1379-1387.
Other Complications of Paget’s Disease
• Osteoarthritis adjacent to affected bones, particularly in the hips
• Fracture (complete, fissure, vertebral compression)
• Neurologic
• Cardiac
• Neoplastic (Rare)Osteosarcoma Rare finding (<1%)
Giant Cell tumors (benign)
![Page 24: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/24.jpg)
Paget’s Disease in the Skull
Courtesy of Pierre Delmas, MD.
Skullenlargement
Dilatedscalpveins
![Page 25: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/25.jpg)
![Page 26: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/26.jpg)
Courtesy of Pierre Delmas, MD.
Early-Stage (Lytic) Paget’s Disease in the Skull:
Known as “Osteoporosis Circumscripta”
Lytic border
![Page 27: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/27.jpg)
Advanced (Sclerotic) Paget’s Disease: “Cotton Wool” Skull
Lyticlesion
Diffuse sclerotic changes
Courtesy of Pierre Delmas, MD.
![Page 28: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/28.jpg)
![Page 29: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/29.jpg)
Complications of Paget’s Disease: Angioid Streak
Crack in Bruch’s membrane, termed “angioid streak”
![Page 30: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/30.jpg)
Paget’s Disease: “Picture Frame” Vertebral Body
Courtesy of Pierre Delmas, MD.
Lytic lesion
Corticalthickening
![Page 31: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/31.jpg)
![Page 32: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/32.jpg)
Courtesy of Pierre Delmas, MD.
Early-Stage (Lytic) Paget’s Disease: Tibia
V-shaped “blade of grass” lesion characteristic of lytic phase of Paget’s disease
![Page 33: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/33.jpg)
![Page 34: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/34.jpg)
![Page 35: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/35.jpg)
Courtesy of Pierre Delmas, MD.
Advanced Paget’s Disease in the Tibia: Sclerotic and Lytic Lesions
Primarily sclerotic changes, with enlargement and thickening of long bones
Secondary osteolytic front
![Page 36: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/36.jpg)
1976
Paget’s Disease: Progression Over 15 Years in Untreated Patient
Courtesy of Pierre Delmas, MD.1991
Bowing
Cortical thickening
![Page 37: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/37.jpg)
Complications of Paget’s Disease: Neoplastic
• Sarcoma (osteosarcoma, chondrosarcoma, fibrosarcoma)
• Benign giant cell tumor
![Page 38: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/38.jpg)
Complications of Paget’s Disease: Osteosarcoma in Pagetic Femur
Reproduced with permission from: N. Kelepouris. Clinical manifestations and diagnosis of Paget's disease of bone. In: Rose, BD (Ed), UpToDate (version 13.3), Waltham, MA 2006. Copyright © 2006 UpToDate, Inc.
Sarcomatous degeneration
![Page 39: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/39.jpg)
![Page 40: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/40.jpg)
Complications of Paget’s Disease: Fissure Fracture in the Tibia
Fissurefracture
![Page 41: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/41.jpg)
![Page 42: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/42.jpg)
Complications of Paget’s Disease: Complete (Chalk-Stick) Fracture in a Femur
Courtesy of Pierre Delmas, MD.
![Page 43: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/43.jpg)
![Page 44: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/44.jpg)
Courtesy of Nuria Guañabens, MD.
Advanced Paget’s Disease in the Pelvis
Bony enlargement
Diffuse sclerotic changes
![Page 45: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/45.jpg)
![Page 46: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/46.jpg)
Courtesy of Nuria Guañabens, MD.
Paget’s Disease in the Femur
Curved deformity of the femur Cortical
thickening
Accentuation of trabecular pattern
![Page 47: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/47.jpg)
Paget’s Disease of Femur
Courtesy of R. Bockman, MD, PhD
X-Ray Bone Scan Pathology
![Page 48: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/48.jpg)
Courtesy of Jacques Brown, MD.
Skeletal Deformities: Bowing of Long Bones
Bowing of humerus
![Page 49: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/49.jpg)
Skeletal Deformities: Bowing of Lower Limbs
Courtesy of Pierre Delmas, MD.
Bowedfemurs
Bowedtibias
![Page 50: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/50.jpg)
A Bone Scan Showing Polyostotic Disease
![Page 51: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/51.jpg)
![Page 52: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/52.jpg)
![Page 53: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/53.jpg)
The Personal Impact of Paget’s Disease
• Self-report survey of 958 persons with Paget’s disease revealed:
–Frequent comorbidities
– Arthritis/arthrosis (64%)
– Hypertension (32%)
– Heart problems (28%)
–Nearly half of patients (47%) reported depression
–44% reported their health as “fair” or “poor”
–Only 21% reported their quality of life was “very good” or “excellent”
Gold DT, et al. J Bone Miner Res. 1996;11:1897-1904.
![Page 54: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/54.jpg)
Managing Paget’s Disease: Bisphosphonates and Other
Treatment Strategies
• Bisphosphonates (gold standard of antipagetic therapy)1-3
• Subcutaneous calcitonin (rarely used)1,2
• Pain management
– NSAIDs, COX-2 inhibitors, analgesics, opioids1,2
• Surgery1,2
– Fractures, bone deformities, osteoarthritis
![Page 55: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/55.jpg)
Indications for Treatment of Paget’s Disease
• Bone pain• Preparation for orthopedic surgery• Fracture of pagetic bone• Hypercalcemia and/or hypercalciuria• Neurologic deficit associated with cranial or
vertebral disease• Presence of high-output congestive heart failure• Prevention of future complications
![Page 56: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/56.jpg)
FDA-Approved Therapies and Dosing Regimens for Paget’s Disease*
Didronel® (etidronate) 5 -10 mg/kg/d or 6 mo
11-20 mg/kg/d 3 mo
3 moSkelid® (tiludronate) 400 mg/d
Fosamax® (alendronate) 40 mg/d 6 mo
Actonel® (risedronate) 30 mg/d 2 mo
Oral agents
Aredia® (pamidronate) 30 mg/d 4 h on 3 cons. days
IV agents
Agent Dose Duration of Therapy
Reclast® (zoledronic acid)
5 mg Single, 15 min.infusion
![Page 57: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/57.jpg)
Effect of Intravenous Pamidronate on Alkaline Phosphatase Activity and Urinary
Hydroxyproline Excretion
![Page 58: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/58.jpg)
Effect on Serum Alkaline Phosphatase of Alendronate 40 mg/day Vs. Placebo or
Etidronate 400mg/day
![Page 59: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/59.jpg)
Biochemical Remission Induced by Risedronate Treatment
Risedronate 30 mg/day x 2 mos.
Etidronate 400 mg/day x 6 mos.
![Page 60: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/60.jpg)
Zoledronic Acid Lowers Alkaline Phosphatase Levels More Than
Risedronate
P < .001
0 10 28 63 91 182Days
0
100
200
300
400
500
To
tal
Alk
alin
e P
ho
sph
atas
e (U
/L)
Mean ( SE) Total Alkaline Phosphatase by Visit
P < .001
P < .001
P < .001 P < .001
Reid IR, et al. N Engl J Med. 2005;353:898-908.Copyright © 2003 Massachusetts Medical Society. All right reserved. Adapted with permission, 2007.
Risedronate 30mg/d x 60d (n=80)
Zoledronic Acid 5mg IV, 15 min (n=121)
Normal alkalinephosphatase range
![Page 61: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/61.jpg)
Mean (± SE) of the absolute value and reference ranges are presented.Adapted from Hosking D, et al. J Bone Miner Res. 2007;22:142-148. With permission of the American Society for Bone and Mineral Research.
During Study Extension, Zoledronic Acid Maintained Mean Serum ALP Better Than
Risedronate
Time From Initiation of Therapy (months)
Ser
um
AL
P (
U/L
)
6 12 18 240
50
100
150
200Start of extendedobservation period
Risedronate 30mg/d x 60d (n=80)
Zoledronic Acid 5mg IV, 15 min (n=121)
Total AlP reference range
![Page 62: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/62.jpg)
Adverse Events With Zoledronic Acid Comparable to Risedronate After Day 3
Zoledronic Acid
(n = 177)
Risedronate (n = 172)
Adverse Events† Patients, n (%) P Value
Total with any AE 117 (66.1) 126 (73.3) .16
Pain in arm or leg 13 (7.3) 12 (7.0) .99
Arthralgia 9 (5.1) 19 (11.0) .05
Dizziness 9 (5.1) 5 (2.9) .41
Nasopharyngitis 9 (5.1) 14 (8.1) .29
Diarrhea 8 (4.5) 9 (5.2) .81
Headache 7 (4.0) 10 (5.8) .46
Back pain 4 (2.3) 12 (7.0) .04
![Page 63: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/63.jpg)
Synthetic Salmon Calcitonin
Dose• 50 to 100 units (0.25-50 ml)/day for 6-18 months or longer, with
repeat course as needed• Subcutaneous or intramuscular injectionSide Effects• Nausea (~10%)• Local irritation at injection site (10%)• Flushed ears and face (10-20%)• Bronchospasm (rare)• Uriticaria (rare)• Anaphylaxis (rare)Drug Resistance• Primary (uncommon)• Secondary: >50% of patients treated >6 months develop
calcitonin antibodies, high titers usually produce resistance (10-20%)
![Page 64: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/64.jpg)
Bisphosphonates• Adverse effects
• UGI intolerance, diarrhea (oral)• Acute phase reaction• Musculoskeletal/bone pain• Hypocalcemia• Renal failure reported with high dose
intravenous bisphosphonates (obtain serum creatinine level before each dose of intravenous bisphosphonate)
• Ocular inflammation (rare)• Osteonecrosis of jaw (ONJ) -rare
• Contraindications• Hypocalcemia• Vitamin D deficiency• Hypoparathyroidism• Severe renal insufficiency
![Page 65: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/65.jpg)
Bisphosphonates, Vitamin D and Calcium
• Correct vitamin D deficiency before administering a bisphosphonate
• Instruct patients to take 1500 mg of calcium and 800 units of vitamin D
(preferably vitamin D3) daily during the 10 days after an infusion of zoledronic acid
![Page 66: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/66.jpg)
Osteonecrosis of Jaw (ONJ) and Bisphosphonates
• Incidence of ONJ – Rare Occurrence with Oral or infrequent IV use as in
Paget’s – Reported in patients not taking bisphosphonates1–3
• ONJ was added to the “Precautions” section of the Prescribing Information for ALL IV and oral bisphosphonates.
• Bisphosphonate-associated ONJ has predominantly occurred in cancer patients receiving IV bisphosphonates4-7
1. Peters E et al. Oral Surg Oral Med Oral Pathol. 1993;75:739–743.2. Erdogan O et al. J Diabetes Complications. 2005;19:364–367.3. Lenz JH et al. J Craniomaxillofac Surg. 2005;33:395–403.4. NIH Osteoporosis and Related Bone Diseases—National Resource Center. Revised November 2005; Available at: www.niams.nih.gov/bone/hi/oralhealth_bone.pdf. 5. Ruggiero S et al. J Oral Maxillofac Surg. 2004;62:527–534.
6. Bamias A et al. J Clin Oncol. 2005;23:8580–8587.7. Woo SB et al. Ann Intern Med. 2006;144:753–761.
![Page 67: Presentation by: Dr. Louis Ricca Clinical Associate Professor of Medicine University of South Florida Diagnosis and Management of Paget’s Disease of Bone](https://reader030.vdocuments.mx/reader030/viewer/2022032707/56649e255503460f94b13a92/html5/thumbnails/67.jpg)
Management Strategies for Osteonecrosis of Jaw
• Patients who develop ONJ during bisphosphonate therapy should receive care by an oral surgeon.
• Management of patients with chronic bone exposure has reportedly included1:• Local irrigation with povidone-iodine and 0.12% chlorhexidine
mouthwash • Oral antibiotics and anti-inflammatory drugs (other pain medications
as needed to control symptoms)• Conservative debridement for necrotic tissue
• Aggressive surgical intervention (such as bone resection) appears counterproductive and may produce further exposed bone.2
• For patients requiring dental procedures (such as surgery), there are no data available to suggest that discontinuation of bisphosphonate treatment reduces the risk for ONJ.
• Current data are not adequate to support that stopping the administration of bisphosphonates is beneficial for improving the outcome of ONJ.1,3
1. Ficarra G et al. J Clin Periodontol. 2005;32:1123–1128.2. Marx RE et al. J Oral Maxillofac Surg. 2005;63:1567–1575. 3. Migliorati CA et al. J Am Dent Assoc. 2005;136:1658–1668.