1121 MUSCULOSKELETAL MANIFESTATIONS OF PAGET’S DISEASE OF BONE ROY D. ALTMAN with the clinical assistance of BARBARA COLLINS A review of 290 patients with Paget’s disease of bone revealed 83% had one or more rheumatic syndromes. The most common finding was back pain (37%)’ most often related to an independent osteoarthritic process or Paget’s disease precipitating or complicating spinal osteoarthritis. Paget’s disease as a sole source of back pain was distinctly uncommon (2%).Osteoarthritis related to Paget’s disease was present in the hip (30%) and knee (11%). Paget’s disease in spondylitis was present in 4 patients and in ankylosing hyperostosis in 4 patients. The latter group had very active Paget’s disease. Rheumatoid arthritis (1%)’ hyperuricemia (20%)’ and gout (4%)did not appear increased in this group. In 1876 Sir James Paget reported “On a Form of Chronic Inflammation of Bones (Osteitis Deformans)” (1). His 5 patients had radicular lower extremity pain, long bone pain, or both. The original patient had a single episode of a synovial effusion of the knee. When the patient died, a pathologic specimen of the femur demonstrated proximal and distal femoral Paget’s disease with femoral head remodeling and osteophyte formation. Paget further stated “In its earlier periods, and sometimes through all its course, the disease is attended From the Arthritis Division, University of Miami, and the Arthritis Section, Miami Veterans Administration Hospital, Miami, Florida. Supported in part by the Clinical Research Unit RR 00261 General Clinical Research Centers Program of Research Sources NIH. Roy D. Altman, MD: Associate Professor of Medicine, Division of Arthritis, University of Miami, Chief, Arthritis Division, Miami Veterans Administration Hospital; Barbara Collins, ARNP. Address reprint requests to Roy D. Altman, MD, University of Miami School of Medicine, P.O. Box 016960, Miami, Florida 33101. Arthritis and Rheumatism, Vol. 23, No. 10 (October 1980) with pains in the affected bones, pains widely various in severity and variously described as rheumatic, gouty, or neuralgic, nor especially nocturnal or periodical.” His second report, 6 years later, included 7 cases (2): 1 was asymptomatic, but the remaining 6 had various rheumatic complaints including ankle pain related to a bowed tibia, back pain, knee pain, gout, and interphalangeal osteoarthritis. In 1936 in a review of 116 cases of Paget’s disease, Gutman and Kasabach reported that pain was present in 77% of their patients, particularly in the leg, lower back, or hips (3). Several reports have related Paget’s disease and osteoarthritis of the hip (4-6) and knee (7). However, not all reports agree with the relationship of Paget’s disease to osteoarthritis (8-11). In a careful review of 55 patients, Franck and coworkers emphasized the common relationship of rheumatic diseases to severely afflicted patients with Paget’s disease (7), documenting many of the clinical manifestations suggested by Sir James Paget. This report is an analysis of 290 patients referred for evaluation of their Paget’s disease. Rheumatic syndromes and Paget’s disease were correlated with clinical, laboratory, roentgenographic, and bone scan parameters. PATIENTS AND METHODS Two-hundred ninety patients were evaluated for Paget’s disease of bone over the period from 1971 to 1980. Characteristics of the population are listed in Table 1. Patients were evaluated with special reference to arthritic and Paget’s disease signs and symptoms. Examination was directed at special problems that may relate Paget’s disease and arthritis, such as abnormal gait and stance, need for ALTMAN 1122 Table 1. Paget’s disease: characteristics of 290 patients Age Sex Race Duration of chief complaint Duration of diagnosis of Paget’s disease Family history of Paget’s disease Renal lithiasis Fractures of pagetic bone Rate Alkaline phosphatase (N<l)* Hydroxyprolenet 67.4 f 8.7 SD years; range 36-91 1.3 men: I woman 286 white: 4 black 6.2 f 7.3 years; range 0-50 9.6 f 9.6 years; range 0-47 42 24 46 1.6/100 patient years 4.7 f 4.7 range 0.4-68.8 228 f 296 mg/24 hr range 4-1486 * Value expressed as finding divided by upper limit of normal range. t Normal range 9-38 mg/24 hr. assisted ambulation, long bone deformity, bone tenderness, functionally short extremity, and range of motion of articulations adjacent to pagetic bones. Laboratory values reviewed included serum alkaline phosphatase in 286 patients, urine hydroxyproline excretion in 130 patients, and serum uric acid in 186 patients. Serum alkaline phosphatase was performed by an automated colorimetric method at the University Medical Center, utilizing a thymolphthalein monophosphate substrate (12). Over the period of the study, there were several changes in the values for the normal range. For this reason, alkaline phosphatase is reported as a multiple of the upper limits of the normal range during the period of collection, i.e. normal <1; elevation > l . These values were recorded prior to pagetic suppressive therapy. Urine hydroxyproline was determined by the modified method of Kivirikko (13). Serum uric acid was performed by an automated colorimetric uricase method in which normal values are less than 8 for men or women (14,15). Total body x-rays were reviewed in 104 patients. X-rays of involved areas of Paget’s disease and/or arthritis were taken in the remainder of the patients. Bone scans were performed in 225, and computer assisted or axial tomography of the spine was reviewed in 34 patients. Narrowing of the radiologic joint space on hip roentgenograms was defined as medial, superior, or superior and medial. The medial refers to a nearly focal defect in the superior medial aspect of the joint just superior to the ligamentum teres. Superior narrowing and superior and medial narrowing correlate respectively to the “superior migration” and “superomedial migration” described by Resnick (16). present in 11%, and pain about the skull often related to vertigo was the primary complaint in 10%. Seven patients had decreased auditory acuity and only 8 patients were seen with no symptoms referrable to the diagnosis of Paget’s disease. The presenting complaint (e.g. pain or decreased hearing) initiated the workup leading to a diagnosis of Paget’s disease in 41% of patients. The remaining patients were diagnosed by x-ray for other purposes (29%), by pursuit of an abnormal alkaline phosphatase value (16%), occasionally by spontaneous fracture through pagetic bone, by clinically apparent skull or long bone deformity, or because a relative had Paget’s disease. Rheumatologic examination revealed signs suggestive of osteoarthritis of one or more joints in 265 patients; e.g. 91% of the patients had crepitus or decreased range of motion of one or more joints. The joints most commonly involved were the cervical spine, shoulder, hip, and knee. Clinical findings suggestive of Paget’s disease were present in 208 (72%). Patients had one or more findings of skull deformity with or without scalp vein distention, pagetic stature or gait, angioid streaks on retinal examination, high output cardiac state, compromised pulmonary reserve, or long bone deformity with or without increased palpable temperature over the involved extremity. Of patients with clinical findings of Paget’s disease, only one such finding above was present in 20%, and five or more of these findings were evident in 11% of patients with an average of 1.8 findings overall. In patients with skull involvement on examination, extensive Paget’s disease was present as exemplified by abnormal “Pagetic stance” in 50%, long bone deformity in 40%, headache in 52%, hearing loss in 46%, dilated scalp veins in 45%, high output cardiac state in 28%, and decreased range of motion of the neck in 75%. Table 2. Paget’s disease: reason for consultation RESULTS Referral was for management of Paget’s disease in 252 patients. However, all but 15 patients had pain that precipitated their consultation (Table 2). Back pain was most common, being the major complaint in 34%, and a secondary complaint in an additional 8 patients (37% total). Back pain was nonspecific and often radicular. Pain around the hip, aggravated by ambulation and relieved by sitting or reclining, was present in 22%. Bone pain associated with long bones or pelvis was Back pain Hip pain Bone pain Headache Knee pain Decreased hearing Neck pain No symptoms Other Total Number of patients (%) Duration years (mean f SD) 98 (34) 65 (22) 33 (11) 29 (10) 19 (6) 7 (2) 5 (2) 8 (3) 27 (9) 7.8 f 9.5 5.0 f 6.0 4.0 f 5.1 7.8 f 6.5 5.4 f 5.5 9.1 -t 9.7 4.0 f 5.6 1.0 f 1.6 6.5 f 7.9 290 (100) 6.2 f 7.6 MUSCULOSKELETAL MANIFESTATIONS About half of the patients who exhibited a pagetic stance had extensive disease with skull enlargement, abnormal gait, and long bone deformities. Half the patients with hearing loss had skull deformity, and half the patients with skull deformity had hearing loss. An abnormal “pagetic stance” was present in 38 (13%) patients who had the waddling gait characteristic of this malady. Abnormal gait related to long bone deformity was present in an additional 25 (9%) patients without pagetic stance. The male predominance was accentuated for those with pelvic Paget’s disease (3.2 men: 1 woman) and reversed in patients with platybasia (1 man: 1.4 women). The mean serum alkaline phosphatase was 4.7 & 4.7 SD times the upper limits of the normal range. A normal alkaline phosphatase value was present in only 12 patients (4.4%). These patients had mostly monostotic disease; however, a few were symptomatic from the involved bones; e.g. calcaneal or navicular foot pain in 2 patients. Table 3 relates the diagnosis of arthritic and pagetic induced pain to serum alkaline phosphatase. The highest elevations of the alkaline phosphatase were present in patients who had pain related to pagetic and arthritic changes about the spine, pagetic changes Table 3. Rheumatic diagnoses and pain syndromes Patients No. (%) Alkaline phosphatase (mean f SD) 50 88 31 18 30 11 4.4 f 2.9 6.6 f 8.6 7.0 f 12.6 45 54 7 4 15 16 19 2 1 5 3.2 f 2.8 10.9 f 12.1 4.4 f 4.2 2.6 f 2.4 7.2 f 5.8 4 1 21.4 f 31.9 4 11 4 13 24 45 8 1 4 1 4 16 3 1.8 f 0.5 8.2 f 9.1 1.5 f 0.5 2.6 f 0.5 5.1 f 4 . 9 4.8 f 4.5 5.1 f 4.9 41 19 33 4 14 7 I1 1 7.2 f 4.6 11.7 f 7.3 6.6 f 12.4 7.8 f 5.0 Lower extremity Long bone pain Hip: DJD* and Paget’s disease Knee: DJD and Paget’s disease Axial skeleton Spine: DJD Spine: DJD and Paget’s disease Spine: Paget’sdisease Spondylitis Ankylosing hyperostosis Ankylosing hyperostosis with Paget’s disease Other rheumatic syndromes Rheumatoid arthritis Gout Chondrocalcinosis Fibrosing syndromes Nonarticular rheumatism InterphalangealDJD Miscellaneous Other pain syndromes Diffuse head pain Platybasia Pelvic pain Miscellaneous ~~~ * DJD = degenerative joint disease. 8 1123 of ankylosing hyperostosis, and skull involvement severe enough to cause platybasia. Bone pain with or without pain from other sources was considered to be present in 135 patients (47%).Bone pain was rarely nocturnal. It was often dull, aching, and aggravated by activities such as weight bearing. Actual bone tenderness was present in only 20 patients. Pain related to platybasia was often localized to the neck and occiput. When this pain was associated with decreased range of motion of the neck, it was difficult to differentiate from cervical osteoarthritis. Pelvic bone pain was particularly difficult to separate from primary or secondary osteoarthritic changes of the hip. A clear definition of the origin of pain was even more difficult in this group when there were abnormalities of the lumbosacral spine. Urine hydroxyproline excretion prior to therapy for Paget’s disease was normal in 10 patients. All 10 had normal serum alkaline phosphatase, as discussed. Degree of hydroxyproline elevation was not dependent upon diagnosis. Lower extremity Long bone deformity was present in 45% of patients. Many of these patients described low back, hip, knee, or ankle pain related to activities. Examination often demonstrated an anterior and lateral bow to the thigh or leg, causing a functional flexion contracture at the knee often in spite of extension at the knee of 0 to - 10”. Increased temperature estimated by palpation of a pagetic limb, particularly the tibia, was present in two-thirds of those patients with long bone deformity. Synovitis and/or crepitus was present in 8 1% of patients with pagetic deformity around the knee, whereas these changes were present in 51% of the patients without juxtaarticular Paget’s disease of the knee. When present, long bone pain was frequently aggravated by activities, i.e. weight bearing. This made the differentiation of long bone pain from arthritis of the hip or knee more difficult unless pain could be localized over a specific area of the long bone. This differentiation was facilitated when pain localized over the site of a radiologic osteolytic wedge. A functionally short extremity was present in 12 patients with bowing of long bones. Pain in one or both hips was present in 88 patients (Table 4). Pain was described in the medial thigh as well as radiating from the trochanteric region. Bone pain from the pelvis or proximal femora was often difficult to differentiate from arthritic pain from the hip. ALTMAN 1124 Table 4. Hip pain and pelvic x-ray changes Number of patients with X-ray of pelvis Pain N o pain Not pagetic -joint space normal Joint space narrow (superior) Pagetic-joint space normal Joint space narrow Superior Medial Superior and medial 0 91 6 4 78 3 6 63 30 0 18 57 26 Total 88 I90 4 This was occasionally facilitated by arthrocentesis of the hip with intrasynovial lidocaine anesthesia. Pain was interpreted to be from osteoarthritis of the hip in 4 patients in whom the hip joint was radiographically normal. Pain was present in 70% of patients with an abnormal roentgenographic joint space. Normal range of motion of the hip was present in 60% of patients with decreased roentgenographic joint space. Full range of motion of the hip was present in 12 patients with pain on exercise or motion of the hip and decreased radiologic joint space. Most radiographic narrowing involved both the medial and superior aspects of the joint space. However, 22 patients had medial joint narrowing with normal superior aspects of the hip joint. One x-ray demonstrated a giant acetabular cyst of the medial ileum and ileopectineal region. Osteophyte formation was present in 40 patients, and 6 patients had protrusio acetabuli. Arthritic changes in the hip by xray were present in 32% of patients with long bone deformity. In 15 patients, there was no adjacent pelvic pagetic change. These patients had superior joint space narrowing. Even in the presence of pelvic Paget’s disease, the bone scan was useful in evaluating the extent of osteoarthritic involvement of the hip. An anterior camera spot view of the hip revealed the following: 1) decreased uptake in the region of the femoral neck indicative of reduced vascular supply to the femoral head, 2) femoral head subchondral bone necrosis with increased uptake of the nuclide that localized to the area of necrosis; this was differentiated from the pelvic uptake in the absence of femoral head Paget’s disease, 3) a diffuse uptake around the hip which suggested a synovitis of the hip in the absence of femoral head Paget’s disease. Examination suggesting osteoarthritis of the knee was present in 144 patients. This was related to distal femoral or proximal tibia1 Paget’s in 31 (22%) patients. In those with pagetic changes around the knee, knee pain was dull and aching, aggravated by activity, and associated with considerable stiffness. Range of motion demonstrated full extension in 16, hyperextension (0 to -10’) in 8, and flexion contractures (+lo” or more) in 7. Incomplete flexion (up to 1 10’) was present in 16. Osteophytes were present in 28 patients and radiologic joint space narrowing was present in all. Knees were stable in anteroposterior and mediolateral planes even if there had been prior medial meniscectomy (4 patients). There was frequent bony deformity such as an enlarged patella, enlarged condyle, or enlarged proximal tibia. Arthroscopy performed on 1 patient with distal femoral pagetic changes revealed an inflammatory synovitis with yellowing of cartilage and deep condylar cartilage fissures without fraying or ulceration. Synovial effusions of the knee were aspirated in 9 patients. Synovianalysis revealed recurrent Type I effusions by criteria of Ropes and Bauer. Microscopically they contained few mononuclear cells and numerous fibrin strands. Synovial effusions remitted in 3 patients after successful chemical suppression of their Paget’s disease. Of patients with knee arthritis and juxtaarticular Paget’s disease, long bone deformity was present in 79%. Assisted ambulation (cane) was needed in 36% of patients with Paget’s disease and related knee arthritis; however, a 76year-old patient with severe distal femoral Paget’s disease related to recurrent knee effusions, knee flexion contractures, and severe pain was able to play handball almost daily. Spine Lumbar spine pain with some evidence of lumbosacral Paget’s disease was the chief complaint in 98 patients (34%) and was significant in an additional 8 patients (37% total). Back pain was nonspecific, often with radiation into both gluteal regions and often into the thighs, legs, or feet. A history suggestive of the cauda equina syndrome was present in 23 patients. Physical findings were often nonspecific, but 38 patients had a typical pagetic stance with straightened lumbar spine, hips, and knees flexed, and paralumbar muscle spasm. Only 49 patients (46%) had physical findings of a positive sciatic stretch sign. If the spine were only partially involved with Paget’s disease, the bone scan could outline pagetic involvement of the neural arch. Routine lumbosacral spine x-rays with obliques did not always define Paget’s disease in the neural arch. Spinal articular facets were only partially defined because many of the patients had osteopenia with minimal apparent sclerosis. Lumbar disc narrowing was present in 36 patients and seemed related to symptoms in 5. Computer assisted or transaxial tomography of 1125 MUSCULOSKELETAL MANIFESTATIONS the lumbar spine was obtained in 34 patients. These techniques helped define arthritic and/or pagetic involvement of the neural arch by accentuating the coarse abnormal trabeculations of Paget’s disease and by defining the size and shape of the articular facets, neural canal, and lateral recesses (medial aspect of the intervertebral foramina). Back pain was considered to be related to solely pagetic changes in the spine in only 7 patients. Lumbar back pain was thought to be related to pagetic combined with arthritic changes in 45 patients where there was distortion of the articular facets and evidence of juxtaposed pagetic bone. Of patients with lumbar pain, 45 (46%) had evidence of arthritis or discogenic disease that did not seem related to the pagetic process. Of patients with pain severe enough to warrant transaxial or computer assisted tomography, abnormalities were moderately severe: 16 had spinal stenosis of at least one level, 8 had a lateral recess syndrome, and 10 had both of these findings. Dorsal spine pain was present in 6 patients with postmenopausal osteopenia related to compression fractures of seemingly nonpagetic bone. One patient had an enlarged dorsal vertebra with spastic paraparesis related to spinal impingement documented by myelography. Marie-Strumpell’s ankylosing spondylitis was present clinically and radiographically in 2 patients. Both had pagetic changes of the spine with pagetic involvement of syndesmophytes. Both had extensive syndesmophyte formation and minimal motion of the spine by examination. Immobility was more significant than pain in both patients. Psoriatic spondylitis was present in 2 of 14 patients with psoriasis. Both patients had pagetic involvement of their lumbar and dorsal spine as well as syndesmophytes. In these 2 patients, immobility was also more significant than pain. No other forms of psoriatic associated arthritis were present in these patients. Ankylosing hyperostosis (diffuse idiopathic skeletal hyperostosis) was recognized in 19 patients. Four of these patients had pagetic changes of the anterior and lateral spinal calcifications. None were symptomatic, but 3 of 4 had significant elevations of their alkaline phosphatase. Dorsal stiffness was present but not clinically significant. Other rheumatic syndromes A history of rheumatoid arthritis was present in 3 patients, but none had active synovitis nor deformity. Two had received chrysotherapy in the past. Rheuma- Table 5. Paget’s disease: serum uric acid of 149 patients ~ Serum uric acid No. of patients Percent Normal range Increase 1 mg% Increase 1-2 mg% Increase 2-3 mg% Increase 3-4 mg% 118 20 8 I 2 19 13 5 1 I toid factor was absent in 2 patients and titered 1 : 80 in 1 patient. An additional patient had Sjogren’s syndrome with mildly active bilateral synovitis of small jointsthis patient was interpreted to have a rheumatoid syndrome associated with Sjogren’s syndrome. A history of gouty arthritis was present in 11 patients. The serum uric acid of patients not on allupurinal is reflected in Table 5. The incidence of hyperuricemia was 20%. Allopurinal was being taken by 24 patients, 4 with a history of gout, and 6 with a history of renal lithiasis. Only one patient had prior identification of uric acid in the synovial fluid; this patient had multiple tophaceous deposits, the only patient with tophaceous gout. Chondrocalcinosis was noted in only 4 patients. No attacks of pseudogout were reported nor recognized. Bursa1 calcification was similarly uncommon, being noted in only 5 patients. Fibrosing syndromes of Dupuytren’s contracture (10 patients-4%) and Peyronie’s disease (4 patients) were noted, but did not seem to relate to the activity of their Paget’s disease. Knuckle pads were present in only 1 patient with Dupuytren’s contracture. An age and sex matched population of 170 patients demonstrated 7 patients with Dupuytren’s contracture (4%). A control population was not available for Peytronie’s disease. Several patients had various forms of nonarticular rheumatism. This included periarthritis (8 patients), carpal tunnel syndrome (5 patients), tendonitis (5 patients), fibrositis (3 patients), epicondylitis (2 patients), and meralgia paresthetica (1 patient). These findings seemed to be independent of their Paget’s disease in most cases. Two patients had periarthritis of the shoulder with scapular or proximal humoral Paget’s disease. Znterphalangeal osteoarthritis was present in 45 patients. This group included 40 women and 5 men and the disease was variable in its manifestations. There was no correlation to the pagetic process. Upper extremity long bone deformity produced special problems. Two patients with humoral bowing were unable to feed or shave themselves with the right hand due to functional extensor contractures related to the deformity. A single patient with marked bowing of ALTMAN 1126 the radius ruptured the fourth and fifth extensor tendors of the extensor digitorium longus, reminiscent of wrist disease in rheumatoid arthritis. Obliteration of the sacroiliac joints was frequently associated with combined sacral and iliac Paget’s disease. No patient seemed to have symptomatic sacroiliitis. DISCUSSION In this review, 242 of 290 (83%) patients referred for evaluation of their Paget’s disease had pain referrable to the musculoskeletal system. There were 396 diagnoses of rheumatic disease or bone pain origin. Pain is a recognized problem in Paget’s disease; in the past, it was classified as neuritic or bony. There have been few reviews emphasizing the rheumatic associations of Paget’s disease. These patients had moderately severe Paget’s disease, based on the fact that they have been referred for evaluation, had moderate or marked elevation of serum alkaline phosphatase and/or urine hydroxyproline, and 97% were symptomatic. For these reasons, our comments on the relation of rheumatic complaints to Paget’s disease should be interpreted in the context of the symptomatic patient with Paget’s disease. Sir James Paget’s original patient had a remodeled femoral head (1). Since that time, there has been question concerning any general relationship between Paget’s disease and osteoarthritis (8- 1 1). Recent radiologic reviews indicate that the overall incidence of osteoarthritis in Paget’s disease may not be increased (10, 1 1); however, the incidence of moderately advanced hip joint narrowing in 43% of our patients seems quite high. As in prior reports (6, lo), there was diffuse medial and superior joint narrowing in the majority of patients, but medial joint narrowing and protrusio acetabuli seemed common. Certainly not all juxtaarticular Paget’s disease was related to osteoarthritic change, but certain factors are believed to influence the normal dynamic and anatomic architecture of the joint. These are: 1 . Juxtaarticular bony enlargement: Pagetic subchondral bone slowly enlarges, similar to pagetic subperiosteal enlargement. Interestingly, cartilage appears to adapt and expand to cover the enlarged subchondral structure. When the normal incongruity of the articular surface is altered, secondary cartilage degeneration may occur (17). Examples of this may be an enlarged femoral head due to Paget’s disease, and enlargement of the ileopectineal line providing medial joint impingement on the femoral head. 2. Altered biodynamics: Bowing and lengthening of lower extremities alter gait and may well alter biodynamic pressure points of juxtaposed cartilage structures without the hip or knee joints (18). A similar process may occur in the spinal apophyseal joints due to localized enlarged pagetic vertebral bone as well as enlarged vertebrae that alter spinal dynamics. 3. Altered subchondral support: Enlargement of subchondral pagetic bone is not necessarily uniform. Uneven expansion provides an uneven base of cartilage support (19). The need for adequate subchondral support has recently been emphasized (20). This uneven support to the cartilage may precipitate osteoarthritic degeneration. The value of radionuclide scanning in rheumatology has recently been reviewed (2 1,22). The presence of pagetic uptake of the nuclide does not obviate the value of bone scanning as discussed. Back pain was the single most common complaint in this series of patients. Paget’s disease, in the author’s opinion, has been given more emphasis than it deserves as cause of back pain (9,23,24). A careful evaluation of the cause of back pain appears appropriate since primary and secondary osteoarthritic changes often complicate the evaluation of pain. In this study, only 7% of patients with back pain were considered to have solely Paget’s disease as the source of their pain. Our findings confirm a prior report of the interesting finding of Paget’s disease in ankylosing spondylitis (10). However, a true increase in Paget’s disease of the spine in ankylosing spondylitis or psoriatic associated spondylitis cannot be clearly concluded from such small numbers of patients. Another interesting finding was the pagetic changes in the spinal calcifications of ankylosing hyperostosis. This was associated with extensive and severe Paget’s disease in 3 of the 4 cases, but was not in itself symptomatic. The occurrence of gout, hyperuricemia, chondrocalcinosis, and rheumatoid arthritis did not seem high, and conflicts somewhat with prior reports (7,25,26). Our findings are consistent with reports of hyperuricemia in the population of the United States (27,28) and chondrocalcinosis in Paget’s disease (29). Dupuytren’s contracture was an interesting finding that did not exceed the incidence in our own population and was even less than that reported in certain population studies (30). However, the finding of Peyronie’s disease in 4 patients may seem high, but no control population was available for comparison. MUSCULOSKELETAL MANIFESTATIONS ACKNOWLEDGMENTS The author is indebted for the clinical assistance of Fred Gargano, MD, Mark Brown, MD, Evelyn Altman, Oscar Gans, to Daphne Stoddart for the preparation of the manuscript, and to David s. Howell, MD for his review of this manuscript. REFERENCES I . Paget J: On a form of chronic inflammation of bones (osteitis deformans). Med Chir Trans 60:37, 1877 2. Paget J: Additional cases of osteitis deformans. Med Chir Trans 65:225, 1882 3. Gutman AB, Kasabach H: Paget’s disease (osteitis deformans). Am J Med Sci 191:361, 1936 4. Machtey I, Rodnan GP, Benedek TG: Paget’s disease of the hip joint. Am J Med Sci 251524, 1966 5. Roper BA: Paget’s disease involving the hip joint-a classification. Clin Orthop Re1 Res 80:33, 1971 6. Goldman AB, Bullough P, Kammerman S, Ambos M: Osteitis deformans of the hip joint. Am J Roentgenol 128:601, 1977 7. Franck WA, Bress NM, Singer FR, Krane SM: Rheumatic manifestations of Paget’s disease of bone. Am J Med 56592, 1974 8. Jaffe HL: The classic Paget’s disease of bone. Clin Orthop Re1 Res 127:4, 1977 9. Milgram JW: Radiographical and pathological assessment of the activity of Paget’s disease of bone. Clin Orthop Re1 Res 127:43, 1977 10. Guyer PB, Dewbury KC: The hip joint in Paget’s disease (Paget’s “coxopathy”). Br J Radio1 51:574, 1978 11. Guyer PB: The clinical relevance of radiologically revealed Paget’s disease of bone (osteitis deformans). Br J Surg 66:438, 1979 12. Roy AV: Rapid method for determining alkaline phosphatase activity in serum with thymolphthalein monophosphate. Clin Chem 16(5):431, 1970 13. Kivirikko KI, Laitinen 0, Prockop DJ: Modifications of a specific assay for hydroxyproline in urine. Anal Biochem 19:249, 1967 14. Praetorius E, Poulsen H: Enzymatic determination of uric acid with detailed directions. Scand J Clin Lab Invest 3:273, 1953 1127 15. Trinder P: Determination of glucose in blood using glucose oxidase with an alternative oxygen acceptor. Ann Clin Biochem 6:24, 1969 16. Resnick D: Patterns of migration of the femoral head in osteoarthritis of the hip-roentgenographic-pathologic correlation and comparision with rheumatoid arthritis. Am J Roentgenol Radium Ther Nucl Med 124:62, 1975 17. Walmsley T: The articular mechanism of the diarthroses. J Bone Joint Surg 10:40, 1928 18. Kaye CF, Lippiello L, Mankin H, Numata T: Evidence for a pressure sensitive stimulus receptor system in articular cartilage. 26th Annual Orthopedic Research Society, Atlanta, Georgia, February 5-7, 1980 19. Freund E: Zur Frage der Ostitis deformans Paget. Virchows Archiv 274:1, 1929 20. Radin EL, Paul IL: Importance of bone in sparing articular cartilage from impact. Clin Orthop Rehab Res 78:342, 197 1 21. Christensen SB, Arnoldi CC: Distribution of 99”’Tc-phosphate compounds in osteoarthritic femoral heads. J Bone Joint Surg 62-A( 1):90, 1980 22. Greyson ND: Radionuclide bone and joint imaging in rheumatology. Bull Rheum Dis 30(7):1034, 1979- 1980 23. Barry HC: Paget’s disease of bone. Edinburgh, E. & S. Livingstone Ltd, 1969, p 33 24. Altman RD, Brown MD, Gargano FP: Transaxial tomography in the assessment of back pain. Arthritis Rheum 21(5):541, 1978 25. Franck WA, Bress NM, Singer FR, Krane SM: Hyperuricemia and gout in Paget’s disease of bone. Arthritis Rheum 17(4):496, 1974 26. Talbott JH, Yii T: Gout and uric acid metabolism. Statton Intercontinental Medical Book Corporation, 1976 27. Mikkelsen WM, Dodge HJ, Valkenburg H: The distribution of serum uric acid values in a population unselected as to gout or hyperuricemia. Am J Med 39:242, 1965 28. Hall AP, Barry PE, Dawber TR, McNamara PM: Epidemiology of gout and hyperuricemia. Am J Med 42:27, 1967 29. Boussina I, Gerster J-C, Epiney J, Fallet GH: A study of the incidence of articular chondrocalcinosis in Paget’s disease of bone. Scand J Rheumatol 5:33, 1976 30. Early PF: Population studies in Dupuytren’s contracture. J Bone Joint Surg 44B:602, 1962 DISCUSSION Dr. Johnston: Have you seen new sites develop during in your followup? We have Seen new lesions ribs, even in patients undergoing therapy. Dr. Altman: We have not noted new lesions even with sequential bone scans. We have used bone scans for following therapy of symptomatic lesions. The bone scan may be the only parameter that changes in the patient with a normal or near normal alkaline phos- phatase such as the calcaneus in one of my patients. Dr. Bijvo& We have found that at times it may take longer to see change in the bone scan than in the alkaline phosphatase values. Dr. Singer: In our patients the Gallium scan has provided a more sensitive parameter of pagetic bone activity than the phosphate scanning agents.