Mod Rheumatol (2007) 17:317–321 DOI 10.1007/s10165-007-0593-8
© Japan College of Rheumatology 2007
ORIGINAL ARTICLE Katsumitsu Arai · Makiko Hoshino · Takehiro Murai Junichi Fujisawa · Naoki Kondo · Takahiro Netsu Hiroshige Sano · Naoto Endo
Proximal femoral fracture in patients with rheumatoid arthritis
Received: February 21, 2007 / Accepted: March 30, 2007
Abstract Hip fracture occurrence was examined crosssectionally in Japanese patients with rheumatoid arthritis (RA). Between January 2005 and June 2006 we studied RA outpatients with a past history of hip fractures. Patients included 1 man and 25 women. As 3 women had bilateral hip fractures, the total number was 29. Age at the time of fracture was 72.1 ± 4.5 years. Of the 29 fractures, 22 were cervical and 7 were trochanteric. Four fractures were spontaneous while the others occurred in falls. 24 fractures were associated with oral steroid administration. All 5 fractures unassociated with prednisolone were cervical. Of the 26 patients, 8 were taking bisphosphonate when fracture occurred. Cervical fracture was treated with total hip arthroplasty in 1 patient whose hip showed RA changes. In others whose hip joint lacked RA change, procedures included osteosynthesis in 2 patients with good function over 6 years; and hemiarthroplasty with a bipolar system in 19 displaced fractures, with good function over 4.1 years. Osteosynthesis was performed for all 7 trochanteric fractures. Trabeculae were thin, and fewer transverse trabeculae could be found in specimens from cervical fracture. Hip fracture in RA patients occurred 10 years earlier than in the general population, and many fractures were cervical. Key words Cervical femoral fracture · Hemiarthroplasty · Hip fracture · Rheumatoid arthritis · Trochanteric femoral fracture
Introduction Evidence of generalized osteoporosis has been reported in patients with rheumatoid arthritis (RA).1–6 While osteopo-
K. Arai (*) · M. Hoshino · T. Murai · J. Fujisawa · N. Kondo · T. Netsu · H. Sano · N. Endo Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Niigata 951-8510, Japan Tel. +81-25-227-2272; Fax +81-25-227-0782 e-mail:
[email protected]
rosis as defined by reduced bone mineral density (BMD) is well known, fracture is the clinically important endpoint in osteoporosis. Symptomatic vertebral compression fracture and hip fracture are both important problems compromising activities of daily living (ADL) and quality of life (QOL). We previously evaluated frequency of vertebral fracture in patients with RA in a cross-sectional and a longitudinal study, concluding that among Japanese RA patients, those over 60 years old and those with BMD below 80% who were treated with a corticosteroid had increased risk of vertebral fracture.5 In a large case–control study from the UK the risk of hip fracture was increased, although not with statistical significance, in RA patients not treated with oral glucocorticoids.6 In primary osteoporosis the incidence of cervical and trochanteric fractures of the proximal femur was shown to be lower in Japan than in Europe or the United States.7–10 We performed the present cross-sectional study to determine the frequency of cervical and trochanteric fractures of the proximal femur among patients with RA.
Patients and methods We studied 26 patients treated in our RA outpatient clinic between January 2005 and June 2006 who had a past history of treatment for cervical or trochanteric fractures of the proximal femur. These patients fulfilled the revised 1987 RA criteria of the American College of Rheumatology.11 There were 1426 patients with RA who were treated in our RA outpatient clinic in the same period. Basic demographic information concerning gender, age, and type of hip fracture was recorded. All hip fractures were classified as being either cervical or trochanteric, with those at the level of the base of the neck included in the trochanteric category. Events precipitating fracture, corticosteroid treatments, given medication for osteoporosis at the time of fracture also were recorded. We also evaluated fracture treatment methods and postoperative follow-up. Patients treated with bipolar
318 Table 1. Age-specific number of proximal femoral fracture in RA patients and general population Age (years)
RA
0–59 60–65 65–70 70–75 75–80 80–85 Older than 85
0 1 7 15 4 2 0
Total
29
(3.4%) (24.1%) (51.7%) (13.8%) (6.9%)
Niigata prefecture 54 (3.2%) 52 (3.1%) 92 (5.4%) 179 (10.5%) 295 (17.4%) 426 (25.1%) 599 (35.3%) 1697
hemiarthroplasty were evaluated further for progression of migration, defined as a change of 3 mm or more in the relationship between the outer head and Kohler’s line, and for vertical and horizontal distances of the center of the outer head from the “tear drop,” as previously described.12,13 A recent series of five resected femoral heads and necks were examined pathologically. These specimens were fixed in 70% alcohol and embedded in methylmethacrylate without decalcification after Villanueva bone staining,14 then cut into sections 5 µm thick. These specimens were compared with the femoral head and neck from RA patients who underwent total hip arthroplasty without fracture.
Results Patients with a past history of treatment for cervical and trochanteric fractures of the proximal femur numbered 26, including 1 man and 25 women. The fracture prevalence of the proximal femur in our RA outpatient clinic between January 2005 and June 2006 was 1.8% (26/1426) in cross section. As 3 female patients had bilateral hip fractures, the total number of fractures was 29. Mean age at time of fracture (± standard deviation) was 72.1 ± 4.5 years. Number of cervical and trochanteric fractures of the proximal femur was 1 among patients 60–65 years old; 7 in those 65–70 years old; 15 in those 70–75 years old; 4 in those 75–80 years old; and 2 in those 80–85 years old (Table 1). Cervical fractures numbered 22 (76%), while trochanteric fractures numbered 7 (24%). Twenty-five fractures occurred during falls, while 4 fractures were spontaneous without a precipitating event. All four of these fractures were cervical, taking place within 8 months after an ipsilateral total knee arthroplasty. Oral steroid therapy was underway at the time of 24 of 29 fractures. Daily dose of prednisolone (Fig. 1) was 10 mg or higher when 2 fractures occurred (both cervical); 20 fractures were associated with 5–9 mg daily (14 cervical, 6 trochanteric); and 2 were associated with 1–4 mg daily (1 cervical, 1 trochanteric). Of the 5 fractures unassociated with prednisolone, all were cervical. Of the 26 patients, 8 were taking bisphosphonate when fracture occurred. Three took alendronate and 5 took etidronate. All 4 patients incurring hip fracture in 2006 were taking bisphosphonate. Among operative methods used for the 22 cervical fractures, osteosynthesis with multiple pinning was performed
Fig. 1. Relationship between the daily dose of prednisolone and occurrence of hip fracture. Five patients without prednisolone therapy nonetheless had cervical fracture
in 2 cases; bipolar hemiarthroplasty in 19 cases; and total hip arthroplasty in 1. In the osteosynthesis cases bony union was complete, and neither displacement of screws nor osteonecrosis occurred during follow-up for a mean of 6 years. Hemiarthroplasty with a bipolar system was considered to be indicated in cases where hip joints showed no radiographic or intraoperative evidence of RA change. Among patients who underwent hemiarthroplasty, none had hip symptoms or migration at the hip during follow-up for a mean of 4.1 years (Fig. 2). Total hip arthroplasty was performed for 1 patient whose affected hip showed Larsen grade II RA change and erosion of the articular surface (Fig. 3). Hip symptoms were abolished by the arthroplasty. Osteosynthesis was performed for all 7 trochanteric fractures, using a compression hip screw system. During a follow-up mean of 4.6 years, only 1 patient developed hip joint RA change (Larsen grade III), associated with hip pain. All cases showed bony union with no displacement of screws. In cervical fracture, trabeculae were thinner and showed more transverse trabecular disappearance with loss of intertrabecular connections than did the femoral neck in hips treated with total hip arthroplasty solely for RA change (Fig. 4). All specimens in five recent cervical fractures showed these findings.
Discussion We cross-sectionally compared the incidence between cervical and trochanteric hip fractures. Our subjects were patients treated in our RA outpatient clinic between January 2005 and June 2006 who had a past history of treatment for cervical or trochanteric fractures of the proximal femur whether at our hospital or another. Incidence of cervical and trochanteric fractures of the proximal femur in 1985,7 1987, 1989,8 1994,9 1999,10 and 2004
319 Fig. 2. Radiography in a 70-year-old woman with rheumatoid arthritis who sustained a cervical fracture of the right femur in a fall (a). After hemiarthroplasty was performed (b), no migration of the prosthesis was observed during 4 years of follow-up (c)
Fig. 3. a,b Radiography in a 69-year-old woman with rheumatoid arthritis. Cervical fracture of the femur occurred spontaneously 3 months after ipsilateral total knee arthroplasty (b). c Total hip arthroplasty was performed considering Larsen grade II RA change and erosion of the articular surface. d No problems with the prosthesis were observed during 2 years and 3 months of follow-up
a
b
a
c
b
d
c
(unpublished data) was evaluated in Niigata prefecture. Overall numbers and incidence of these cervical and trochanteric hip fractures increased during the study period. In 1999, the number of cervical or trochanteric fractures of the proximal femur was 92 in persons 65–69 years old; 179 in those 70–74 years old; 295 in those 75–79 years old; 426 in those 80–84 years old; and 599 in persons older than 85 years. The peak age in the general population at the time of cervical or trochanteric fracture of the proximal femur was over 85 years old (Table 1). Among the RA patients presently studied mean age at fracture (± standard deviation) was 72.1 ± 4.5 years, with a peak age of 70–75 years,
about 10 years younger than in the general population. This difference may reflect osteoporosis associated with RA itself, with steroid treatment, or with loss of activity. Our five patients receiving no steroids all had cervical fractures. In large studies, Staa et al.6 and Cooper et al.15 found that RA patients not taking oral glucocorticoids also had increased risks of fracture, most likely resulting from the disease process of RA. Staa et al.6 prospectively evaluated 30 262 patients in the UK with RA, of whom 2460 incurred a fracture during a median follow-up of 7.6 years. Patients with RA had an increased risk of fracture compared with controls, particularly the hip [relative risk (RR) 2.0; 95%
320 Fig. 4a–c. Histopathologic findings in a 65-year-old woman with cervical neck fracture. a Trabeculae were thinner and transverse trabeculae were fewer with loss of connections between trabeculae (b) compared with the cervical neck in a 51-year-old RA patient without fracture who underwent total hip arthroplasty for RA change (c) (Villanueva bone staining, ×20)
a
confidence interval (95% CI) 1.8–2.3] and spine (RR, 2.4; 95% CI, 2.0–2.8). Indicators of a substantially elevated risk of hip fracture included duration of RA exceeding 10 years (RR, 3.4; 95% CI, 3.0–3.9); low body mass index (BMI; RR, 3.9; 95% CI, 3.1–4.9); and treatment with oral glucocorticoids (RR, 3.4; 95% CI, 3.0–4.0). Huusko et al.16 reported that age and sex-adjusted risk of hip fractures was increased by RA in central Finland (RR, 3.26; 95% CI, 2.26–4.70). In our present evaluation of hip fractures, cervical fractures accounted for 76% and trochanteric fractures for 24%. In persons with primary osteoporosis in Niigata Prefecture,10 relative frequency of cervical fracture was 37% and trochanteric fractures, 63%. Decreases in cancellous bone were associated with trochanteric fracture, while decreased cortical bone was associated with cervical fracture.17 Cortical thinning occurs with aging by endocortical resorption and loss of femoral trabecular bone mineral density, which was studied by peripheral quantitative computed tomography.18 We previously reported two-dimensional strut analyses of the structure of iliac bone biopsies in 40 postmenopausal women with RA as compared to specimens with 40 agematched primary osteoporosis.1 The two-dimensional parameters of trabecular structure were measured according to the methods of Garrahan et al.19 and Mellish et al.20 Trabecular thickness and wall thickness declined with age; changes were particularly accelerated by glucocorticoids. Connectivity of cortical bone to nodes (Ct.Nd) and cortical thickness significantly decreased with age; glucocorticoid therapy accelerated disappearance of the nodes. In vertebral compression fractures, both node to node (Nd.Nd) and Ct.Nd connectivity decreased significantly. Because of sitespecific differences, we could not compare proximal femoral specimens from RA patients with primary osteoporosis specimens from sites like the iliac crest. Instead, we compared femoral neck fracture specimens with total hip arthroplasty specimens in RA, finding trabecular thickness at fracture sites to be less and transverse trabeculae to be fewer, with greater loss of trabecular connections. Bisphosphonate administration has been reported to reduce the risk of hip fracture.21–23 In the present study, all four patients treated for hip fracture in 2006 were receiving
b
c
bisphosphonate. A large controlled study concerning fracture prevention by bisphosphonate in RA patients is needed. Among our patients, four fractures occurred spontaneously; all four were cervical and occurred within 8 months after ipsilateral total knee arthroplasty. Subcapital stress fracture of the femoral neck has been described in association with pathologic changes of RA or osteoporosis, and in patients with prolonged steroid treatment.24 Changes in the weight-bearing axis of the extremity after total knee arthroplasty in patients with large deformities of the knee are likely to concentrate distraction forces in the superior cortex of the femoral neck. In treatment of the rheumatoid hip, hemiarthroplasty with a bipolar system has had unsatisfactory results, with central migration.25,26 Bogoch and Moran27 reported that although 90% of cases of femoral neck fracture in patients with RA occur in a hip with a relatively intact articular cartilage surface, the high rate of fixation failure in displaced femoral neck fractures requires consideration of prosthetic arthroplasty. However, no definitive total hip arthroplasty with hemiarthroplasty in RA patients with fracture comparing study is available.27 Only in hips with displaced cervical neck fracture and no radiographically or intraoperatively evident RA change did we consider bipolar hemiarthroplasty to be indicated. Among our patients who underwent hemiarthroplasty, all had no hip-related symptoms over 4.1 years of follow-up, in agreement with previous Japanese experience.13,28 On the other hand, total hip arthroplasty was chosen in one patient whose hip joint showed Larsen grade II RA change and erosion of the articular surface. Thus, hemiarthroplasty with a bipolar system appears to have good intermediate-term results in cervical fracture cases without RA, but longer follow-up will be important in determining optimal treatment.
References 1. Hanyu T, Arai K, Takahashi HE. Structural mechanisms of bone loss in iliac biopsies: comparison between rheumatoid arthritis and postmenopausal osteoporosis. Rheum Int 1999;18:193–200.
321 2. Kanis JA, Johansson H, Oden A, Johnell O, de Laet C, Melton III LJ, et al. A meta-analysis of prior corticosteroid use and fracture risk. J Bone Miner Res 2004;19:893–9. 3. Ørstavik RE, Haugeberg G, Mowinckel P, Hoiseth A, Uhlig T, Falch JA, et al. Vertebral deformities in rheumatoid arthritis: a comparison with population-based controls. Arch Intern Med 2004;164:420–5. 4. de Nijs RN, Jacobs JW, Bijlsma JW, Lems WF, Laan RF, Houben HH, et al. Osteoporosis Working Group, Dutch Society for Rheumatology. Prevalence of vertebral deformities and symptomatic vertebral fractures in corticosteroid treated patients with rheumatoid arthritis. Rheumatology 2001;40:1375–83. 5. Arai K, Hanyu T, Sugitani H, Murai T, Fujisawa J, Nakazono K, et al. Risk factors for vertebral fracture in menopausal or postmenopausal Japanese women with rheumatoid arthritis: A crosssectional and longitudinal study. J Bone Miner Metab 2006;24: 118–24. 6. Staa TP, Geusens P, Bijlsma JWJ, Leufkens HGM, Cooper C. Clinical assessment of the long-term risk of fracture in patients with rheumatoid arthritis. Arthritis Rheum 2006;54:3104–12. 7. Kawashima T. Epidemiology of the femoral neck fracture in 1985, Niigata Prefecture, Japan. J Bone Miner Metab 1989;7:118–26. 8. Dohmae Y, Takahashi HE, Kawashima T. Epidemiology of femoral neck fracture in 1989, Niigata Prefecture, Japan. A comparison with the incidence in 1985 and 1987. J Bone Miner Metab 1991;9:94–8. 9. Iga T, Dohmae Y, Endo N, Takahashi HE. Increase in the incidence of cervical and trochanteric fractures of the proximal femur in Niigata Prefecture, Japan. J Bone Miner Metab 1999;17: 224–31. 10. Morita Y, Endo N, Iga T, Tokunaga K, Ohkawa Y. The incidence of cervical and trochanteric fractures of proximal femur in 1999 in Niigata Prefecture, Japan. J Bone Mineral Metab 2002;20:311–8. 11. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988;31:315–24. 12. Gates HS, Poletti SC, Callaghan JJ, McCollum DE. Radiographic measurements in protrusion acetabuli. J Arthloplasty 1989;4: 347–51. 13. Sano T, Mori T, Yamada N, Yoshida S, You S, Watanabe S, et al. Bipolar hemiarthroplasty for femoral neck fractures in rheumatoid arthritis (in Japanese). Jpn J Rheum Joint Surg 2003;22: 123–30. 14. Villanueva AR. A bone stain for osteoid seams in fresh, unembedded, mineralized bone. Stain Technol 1974;49:1–8.
15. Cooper C, Coupland C, Mitchell M. Rheumatoid arthritis, corticosteroid therapy and hip fracture. Ann Rheum Dis 1995;54:49–52. 16. Huusko TM, Korpela M, Karppi P, Avikainen V, Kautiainen H, Sulkava R. Threefold increased risk of hip fractures with rheumatoid arthritis in Central Finland. Ann Rheum Dis 2001;60:521–2. 17. Bell KL, Loveridge N, Power J, Rushton N, Reeve J. Intracapsular hip fracture: increased cortical remodeling in the thinned and porous anterior region of the femoral neck. Osteoporos Int 1999; 10:248–57. 18. Horikoshi T, Endo N, Uchiyama T, Tanizawa T, Takahashi HE. Periphearal quantitative computed tomography of the femoral neck in 60 Japanese women. Calcif Tissue Int 1999;65:447–53. 19. Garrahan NJ, Mellish RWE, Compston JE. A new method for the two-dimensional analysis of bone structure in human iliac crest biopsies. J Microsc 1986;142:341–9. 20. Mellish RWE, Ferguson-Pell MW, Cochran GVB, Lindsay R, Dempster DW. A new manual method for assessing twodimensional cancellous bone structure: comparison between iliac crest and lumbar vertebra. J Bone Miner Res 1991;6:689–96. 21. Cranney A, Guyatt G, Griffith L, Wells G, Tugwell P, Rosen C. Metaanalysis of therapies for postmenopausal osteoporosis. IX: Summary of meta-analysis of therapies for postmenopausal osteoporosis. Endocr Rev 2002;23:570–8. 22. Papapoulos SE, Quandt SA, Liberman UA, Hochberg MC, Thompson DE. Meta-analysis of the efficacy of alendronate for the prevention of hip fractures in postmenopausal woman. Osteoporos Int 2005;16:468–74. 23. Cranney A, Tugwell P, Adachi J, Weaver B, Zytaruk N, Papaioannou A. Meta-analysis of the therapies for postmenopausal osteoporosis. III. Meta-analysis of risedronate for the treatment of postmenopausal osteoporosis. Endocr Rev 2002;23:517–23. 24. Joshi N, Pidemunt G, Carrera L, Navarro-Quilis. A Stress fracture of the femoral neck as a complication of total knee arthroplasty. J Arthroplasty 2005;20:392–5. 25. McConville OR, Bowman AJ, Kilfoyle RM, McConville JF, Mayo RA. Bipolar hemiarthroplasty in degenerative arthritis of the hip100 consecutive cases. Clin Orthop 1990;251:67–74. 26. Vazquez-Vela G, Vazquez-Vela E, Dobarganes FG. The bateman bipolar prosthesis in osteoarthritis and rheumatoid arthritis-a review of 400 cases. Clin Orthop 1990;251:82–6. 27. Bogoch ER, Moran EL. Bone abnormalities in the surgical treatment of patients with rheumatoid arthritis. Clin Orthop 1999;366: 8–21. 28. Kageyama Y, Miyamoto S, Ozeki T, Shimazu M, Inoue T. A study of bipolar-type hip arthroplasty for rheumatoid arthritis (in Japanese). Jpn J Rheum Joint Surg 1994;13:277–82.