JBJS | An Outcome Study of Chronic Patellofemoral Pain Syndrome. Seven-Year Follow-up of Patients in a Randomized, Controlled Trial*

The Journal of Bone & Joint Surgery, Volume 81, Issue 3

Articles | March 01, 1999

An Outcome Study of Chronic Patellofemoral Pain Syndrome. Seven-Year Follow-up of Patients in a Randomized, Controlled Trial*

PEKKA KANNUS, M.D., PH.D.†; ANTERO NATRI, M.D., PH.D.‡; TIMO PAAKKALA, M.D., PH.D.§; MARKKU JÄRVINEN, M.D., PH.D.§, TAMPERE, FINLAND

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Investigation performed at the UKK Institute and Tampere University Hospital, Tampere

The Journal of Bone & Joint Surgery. 1999; 81:355-63

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Abstract

Background: We determined prospectively the long-term outcomes of nonoperative treatment of chronic patellofemoral pain syndrome.Methods: Of forty-nine patients in a prospective, randomized, double-blind study of unilateral chronic patellofemoral pain syndrome in the knee, forty-five were reexamined seven years after the initial trial of treatment. In the earlier trial, the short-term (six-month) effects of intra-articular injections of glycosaminoglycan polysulfate combined with intensive quadriceps-muscle exercises were compared with those of injections of a placebo combined with exercises and with those of exercises alone. At seven years, the follow-up consisted of standardized subjective, functional, and clinical assessments and muscle-strength measurements as well as magnetic resonance imaging, radiography, and bone-densitometry measurements of the knee.Results: At six months, complete subjective, functional, and clinical recovery had occurred in almost three-fourths of the patients and, with the numbers available for study, neither significant nor clinically important differences among the three initial treatment groups were detected. The subjective and functional parameters showed few changes between six months and seven years; almost three-fourths of the patients still had full subjective and functional recovery at the time of the latest follow-up. However, according to the physician's clinical evaluation, the number of patients who had no symptoms on the patellar compression and apprehension tests decreased over time, from forty-two (93 percent) and forty (89 percent) of forty-five patients at six months to thirty (67 percent) and thirty-one (69 percent) at seven years; these changes were significant (p = 0.002 and p = 0.023, respectively). The number of patients who had crepitation on the patellar compression test increased over time, from twenty-six (58 percent) at six months to thirty-six (80 percent) at seven years (p = 0.021). The physician's overall assessment showed a similar trend, with thirty-four patients (76 percent) having had complete recovery at six months compared with thirty (67 percent) at seven years; however, with the numbers available, this change was not significant (p = 0.420). Magnetic resonance imaging, performed for thirty-seven patients, revealed no abnormalities in twenty-four (65 percent), mild abnormalities in four (11 percent), moderate abnormalities (a 25 to 75 percent decrease in the thickness of the cartilage) in seven (19 percent), and overt patellofemoral osteoarthritis in two (5 percent) at seven years.Conclusions: The seven-year overall outcome was good in approximately two-thirds of the patients. However, the remaining patients still had symptoms or objective signs of a patellofemoral abnormality.

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Introduction

Introduction | Materials and Methods | Results | Discussion | References

Patellofemoral pain syndrome is characterized by retropatellar pain and crepitation during activities such as squatting, going up or down stairs, running, and jumping. Patellar pseudolocking, a snapping sensation, stiffness of the knee, and effusions also may occur. Patellofemoral pain syndrome is frequently seen in young adults^11,18,35. In clinics that manage patients who have musculoskeletal syndromes, patellofemoral pain syndrome may account for almost 10 percent of all visits (seventy-six of 814 in one study¹⁷) and for 20 to 40 percent of all knee problems (seventy-six of 266¹⁷).

One form of pathological change in the articular cartilage of the patella, chondromalacia of the patella, is characterized by macroscopic softening, fissuring, and fragmentation, which can cause retropatellar pain and crepitation during activities that load the patellofemoral joint^11,18,34,35. In addition, cartilage damage frequently occurs at a microscopic level and takes the form of degradation and softening of the cartilaginous matrix^13,18,34,37. However, retropatellar pain and crepitation also may occur during similar activities or during compression of the patella in association with rubbing against the femoral condyles, in the absence of evidence of cartilage damage^{10,13,24,36,38}.

The relationship between patellofemoral pain syndrome and chondromalacia is controversial. Some studies have demonstrated involvement of the patellar articular cartilage with use of arthroscopy in asymptomatic individuals^5,10,16,36. In other studies, normal cartilage has been observed arthroscopically in many patients who had clearly apparent symptoms and abnormal radiographic findings^20,24,45. Furthermore, some investigators have found no relationship between the extent of macroscopic cartilaginous lesions and the severity of symptoms^{7,14,25,41,42}.

Although the etiology and pathogenesis of patellofemoral pain syndrome are poorly understood, many predisposing factors, including acute trauma, overuse, immobilization, excessive weight, genetic predisposition, malalignment of the knee-extensor mechanism, congenital anomalies of the patella, prolonged synovitis, recurrent hemorrhage into a joint, joint infection, and repetitive intra-articular injection of corticosteroids, have been proposed^{2,11,18,35,38}. In many patients, however, there is no apparent reason for the symptoms^6,13,18,46.

Once it has begun, patellofemoral pain syndrome frequently becomes chronic, and the pain may force the patient to limit physical activities. It has been suggested that patellofemoral pain syndrome may lead to patellofemoral osteoarthritis^10,13,31,46, but there is a lack of prospective studies with long-term follow-up and reliable evidence.

The purpose of the current study was to determine the long-term outcome and the prognosis for patients who received nonoperative treatment for chronic patellofemoral pain syndrome. We evaluated the seven-year results of a randomized, double-blind trial in which the short-term (six-month) efficacy of a specific drug therapy (glycosaminoglycan polysulfate) had been compared with that of a placebo and with that of quadriceps-muscle exercises¹⁸. The present study was designed to assess the long-term subjective, functional, and clinical outcomes and to analyze the radiographic, magnetic resonance imaging, and bone-densitometry findings.

*No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. Funds were received in total or partial support of the research or clinical study presented in this article. The funding source was the Medical Research Fund of Tampere University Hospital, Tampere, Finland.

†Accident and Trauma Research Center, UKK Institute, Kaupinpuistonkatu 1, FIN-33500 Tampere, Finland. E-mail address: klpeka@uta.fi.

‡Tampere Research Center of Sports Medicine, UKK Institute for Health Promotion Research, P.O. Box 30, FIN-33501 Tampere, Finland.

§Departments of Radiology (T. P.) and Surgery (M. J.), Tampere University Hospital, P.O. Box 2000, FIN-33521 Tampere, Finland.

†Accident and Trauma Research Center, UKK Institute, Kaupinpuistonkatu 1, FIN-33500 Tampere, Finland. E-mail address: klpeka@uta.fi.

‡Tampere Research Center of Sports Medicine, UKK Institute for Health Promotion Research, P.O. Box 30, FIN-33501 Tampere, Finland.

§Departments of Radiology (T. P.) and Surgery (M. J.), Tampere University Hospital, P.O. Box 2000, FIN-33521 Tampere, Finland.

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FIG1:: Fig. 1 A: Graph showing changes in the pain scores, as assessed by the patients with use of a 100-millimeter visual-analog scale (VAS). B: Graph showing changes in the scores according to the scale described by Lysholm and Gillquist²⁷. C: Graph showing changes in the scores according to the scale described by Tegner et al.⁴³. The values for the forty-five patients are given as the mean and the 95 percent confidence interval. The improvements in the three scores were highly significant between the baseline (BL) and seven-year evaluations (p < 0.001 for each); however, with the numbers available, the changes between six months and seven years were not found to be significant (p = 0.16, 0.73, and 0.079, respectively).

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FIG2:: Fig. 2 Bar graph showing the deficit in the extension strength of the affected knee compared with the strength of the contralateral, unaffected knee. The values for the forty-five patients are given as the mean and the 95 percent confidence interval. The improvement was highly significant between the baseline and seven-year evaluations (p = 0.001); however, with the numbers available, the change between six months and seven years was not found to be significant (p = 0.22).

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TABLE I NUMBER OF PATIENTS WHO WERE ASYMPTOMATIC ON FUNCTIONAL TESTS OF THE KNEE*

*The values are based on a total of forty-five patients. †According to the McNemar test.

Test	Baseline Evaluation	At 6 Mos.	At 7 Yrs.	P Value for Difference Between 6 Mos. and 7 Yrs.†
Hopping with affected limb	0	35 (78%)	34 (76%)	1.000
Duck-walking	0	39 (87%)	36 (80%)	0.380
25-repetition full-squat	0	32 (71%)	32 (71%)	1.000

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TABLE I NUMBER OF PATIENTS WHO WERE ASYMPTOMATIC ON FUNCTIONAL TESTS OF THE KNEE*

*The values are based on a total of forty-five patients. †According to the McNemar test.

Test	Baseline Evaluation	At 6 Mos.	At 7 Yrs.	P Value for Difference Between 6 Mos. and 7 Yrs.†
Hopping with affected limb	0	35 (78%)	34 (76%)	1.000
Duck-walking	0	39 (87%)	36 (80%)	0.380
25-repetition full-squat	0	32 (71%)	32 (71%)	1.000

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TABLE II NUMBER OF PATIENTS WHO WERE ASYMPTOMATIC ON THE PATELLAR COMPRESSION AND APPREHENSION TESTS, HAD NO CREPITATION ON THE COMPRESSION TEST, AND HAD COMPLETE RECOVERY ACCORDING TO THE PHYSICIAN'S ASSESSMENT*

*The values are based on a total of forty-five patients. †According to the McNemar test.

	Baseline Evaluation	At 6 Mos.	At 7 Yrs.	P Value for Difference Between 6 Mos. and 7 Yrs.†
No symptoms on patellar tests
Compression	0	42 (93%)	30 (67%)	0.002
Apprehension	0	40 (89%)	31 (69%)	0.023
No crepitation on patellar compression test	0	19 (42%)	9 (20%)	0.021
Complete recovery as determined by physician	0	34 (76%)	30 (67%)	0.420

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*The values are based on a total of forty-five patients. †According to the McNemar test.

	Baseline Evaluation	At 6 Mos.	At 7 Yrs.	P Value for Difference Between 6 Mos. and 7 Yrs.†
No symptoms on patellar tests
Compression	0	42 (93%)	30 (67%)	0.002
Apprehension	0	40 (89%)	31 (69%)	0.023
No crepitation on patellar compression test	0	19 (42%)	9 (20%)	0.021
Complete recovery as determined by physician	0	34 (76%)	30 (67%)	0.420

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TABLE III RELATIVE DEFICITS IN BONE-MINERAL DENSITY (GRAMS PER SQUARE CENTIMETER) IN THE AFFECTED KNEE COMPARED WITH THE CONTRALATERAL, UNAFFECTED KNEE

*Bone-densitometry measurements were available for forty-two patients; however, two patients had clear evidence of subchondral sclerosis in the patella and thus reliable measurements could not be made at that site. †The values are given as the mean and the standard deviation, with the 95 percent confidence interval in parentheses. The percent difference was calculated according to the equation: 100% x (bone-mineral density in the affected knee - bone-mineral density in the unaffected knee)/bone-mineral density in the unaffected knee. ‡According to the matched, paired t test.

Site*	Percent Difference† (Grams per Square Centimeter)	P Value‡
Distal part of femur (n = 42)	-3.3 ± 5.9 (-5.1 to -1.4)	0.001
Patella (n = 40)	-2.5 ± 6.7 (-4.7 to -0.4)	0.020
Proximal part of tibia (n = 42)	-2.0 ± 4.2 (-3.3 to -0.7)	0.003

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TABLE III RELATIVE DEFICITS IN BONE-MINERAL DENSITY (GRAMS PER SQUARE CENTIMETER) IN THE AFFECTED KNEE COMPARED WITH THE CONTRALATERAL, UNAFFECTED KNEE

Site*	Percent Difference† (Grams per Square Centimeter)	P Value‡
Distal part of femur (n = 42)	-3.3 ± 5.9 (-5.1 to -1.4)	0.001
Patella (n = 40)	-2.5 ± 6.7 (-4.7 to -0.4)	0.020
Proximal part of tibia (n = 42)	-2.0 ± 4.2 (-3.3 to -0.7)	0.003

Materials and Methods

Introduction | Materials and Methods | Results | Discussion | References

Patient Population, Randomization, and Treatment Regimens

The criteria for initial inclusion in the study, which were based on previous studies of patellofemoral pain syndrome^6,22,25,47, included (1) an age between fifteen and fifty years, with closed epiphyseal growth plates; (2) no general illnesses or use of medication; (3) a characteristic history and symptoms of patellofemoral pain syndrome in one knee (at least a two-month duration of retropatellar pain during physical activities such as jumping, running, squatting, and going up or down stairs; patellar crepitation during squatting; retropatellar pain when the knee is kept in flexion for a prolonged period, with relief on extension; and, possibly, patellar snapping, pseudolocking, giving-way, stiffness, or periodic effusions in conjunction with physical activity); (4) characteristic clinical signs of patellofemoral pain syndrome in one knee (retropatellar pain and crepitation in association with patellar compression, grinding, or apprehension tests as well as retropatellar pain in association with one-limb squatting); (5) no evidence of other abnormalities, such as ligamentous instability or a meniscal tear, on physical examination of the knee; and (6) no abnormalities indicative of osteoarthritis, osteochondritis dissecans, loose bodies, or other related abnormalities on anteroposterior or lateral weight-bearing radiographs, a tunnel radiograph, or a tangential radiograph of the patella, made with the knee in 30 degrees of flexion.

Fifty-three consecutive patients (twenty-five men and twenty-eight women) who were seen at our clinic because of a characteristic unilateral patellofemoral pain syndrome were asked to participate in the trial. None of them refused. The mean age (and standard deviation) was 27 ± 9 years, and the mean duration of the symptoms before the beginning of the study was 16 ± 19 months. The right knee was involved in thirty-one patients, and the left knee was involved in twenty-two.

Patients were excluded from the study if they had ever received any kind of injection for the condition or if they had taken nonsteroidal anti-inflammatory drugs or had received physical therapy within the previous thirty days. Other criteria for exclusion were pregnancy; breast-feeding; and any contraindications to glycosaminoglycan polysulfate, lidocaine, or nonsteroidal anti-inflammatory drugs.

All subjects were informed of the study procedure, the purpose of the study, and any known risks, and all gave informed consent. The study was conducted in conformity with the principles of the Helsinki II Declaration and was approved by the Committee of Ethics on Human Research at our clinic.

The clinical and radiographic methods of evaluation that were used initially have been described previously¹⁸. Seventeen patients had had arthroscopy because of persistent patellar pain and crepitation before they were enrolled in the initial study¹⁸. Eight of these patients had pathological changes in the patellar cartilage. None of the fifty-three patients had magnetic resonance imaging studies initially.

After the initial clinical and radiographic evaluations had been performed and the strength of the quadriceps had been assessed, the patients were randomized, with use of sealed envelopes, into one of three treatment groups. Patients in Group A were managed nonoperatively for six weeks, with elimination of all pain-producing activities, use of intensive isometric exercises for the quadriceps muscle once a day, and oral administration of nonsteroidal anti-inflammatory drugs (twenty milligrams of piroxicam each morning for twenty days). Patients in Group B received the same nonoperative treatment and five intra-articular injections (once a week) of a placebo consisting of one milliliter of physiological saline solution combined with one milliliter of lidocaine solution (ten milligrams per milliliter). Patients in Group C were managed in the same way as those in Group B, except that one milliliter of glycosaminoglycan polysulfate solution (fifty milligrams per milliliter) was used instead of the saline solution. These treatment regimens have been reported in detail previously¹⁸.

With use of less than a 5 percent probability of a type-I error (p < 0.05) and a power of 80 percent (type-II error, 0.20), a sample size of forty-eight patients (sixteen patients per group) was necessary to detect a 90 percent overall success rate in the group that received glycosaminoglycan polysulfate when a 50 percent success rate in the control groups was predicted³⁰.

Outcome Assessments

Each patient was examined by the same two of us (P. K. and A. N.) at the time of enrollment in the study, after six months, and after seven years. The mean duration of follow-up was 6.6 ± 1.3 years from the beginning of the treatment and 7.9 ± 1.9 years from the onset of the symptoms.

Subjective Evaluation

Pain and discomfort during activities were recorded with use of the classic 100-millimeter visual-analog scale, with 0 points indicating no pain and 100 points, extremely intense pain^1,25. At the six-month and seven-year follow-up visits, an additional 5-point scale was used to classify the subjective overall assessment, with 1 point indicating a completely asymptomatic knee and 5 points, a knee that had worse symptoms than before the treatment.

Functional Evaluation

The functional evaluation of the knee was performed with use of the standardized scoring scales described by Lysholm and Gillquist²⁷ and by Tegner et al.⁴³. The scale described by Lysholm and Gillquist, which ranges from 0 to 100 points (best score, 100 points), is used to evaluate pain, swelling, and giving-way of the knee during activity; the ability to squat and to climb stairs; the presence of a limp and the need for support while walking; and the amount of atrophy of the quadriceps. The scale described by Tegner et al., which assigns a score ranging from 0 to 10 points (best score, 10 points), is employed to assess the ability to work and exercise with use of the affected knee, with 0 points indicating that no physical activity of any kind is possible and 10 points, that all kinds of activities, including very strenuous athletic training at peak levels, are possible.

The isometric strength of the quadriceps muscle was measured with the knee in 60 degrees of flexion (full extension is equal to 0 degrees), with use of a standardized isometric dynamometer (Digitest, Muurame, Finland)^18,37, at the time of the initial examination and at the six-month and seven-year follow-up visits. Three maximum efforts were allowed, and the best result was recorded. For each subject, the value for the unaffected side was used as the reference point.

Three additional functional evaluations were performed¹⁸. For two of them, a 4-point scale was used to evaluate the ability to hop with use of the affected limb and to duck-walk (walk forward while in a full squatting position), with 1 point indicating that the activity could be performed without difficulty or pain and 4 points, that the activity could not be performed because of intense pain. The third test was a twenty-five-repetition full-squat test to evaluate pain, with 1 point indicating that the patient could not squat without pain; 2 points, that the patient could perform one to five squats; 3 points, that the patient could perform six to ten squats; and 7 points, that the patient could perform more than twenty-five squats without pain.

Clinical Evaluation

At the time of the visits to the clinic, three patellofemoral parameters were evaluated. These included pain during the patellar compression test, pain during the patellar apprehension test (in which the patient tightens the quadriceps muscle with the knee extended while the examiner prevents the patella from moving upward), and crepitation during the compression test^9-11,26. These tests were scored with use of a 4-point scale, with 1 point indicating no pain or crepitation and 4 points, intense pain or crepitation.

The physician's opinion of the effect of treatment at six months and seven years was assessed with use of a 5-point scale, with 1 point indicating complete subjective, functional, and clinical recovery and 5 points, that the overall status was worse than it had been before the treatment.

Magnetic Resonance Images and Radiographs

None of the patients had magnetic resonance imaging studies initially. At the seven-year follow-up evaluation, the outcome was assessed with use of magnetic resonance images and plain radiographs of the involved and contralateral knee joints. Special attention was paid to the patellofemoral joint with regard to both early and advanced signs of osteoarthritis^{11,23,28,32,33,38,48}. These analyses were performed by one of us (T. P.), a radiologist, on a blind basis (that is, the examiner did not know whether the magnetic resonance images and radiographs were those of the affected or the unaffected knee).

The magnetic resonance imaging was performed with the use of a 0.5-tesla superconducting magnetic-resonance-imaging unit (Gyroscan T5; Philips Medical Systems, Best, The Netherlands). In addition to the routine axial (transverse) and sagittal T1-weighted spin-echo and T2-weighted turbo-spin-echo sequences, axial and sagittal fat-suppression T2-weighted images (turbo-spin-echo images with spectral presaturation with inversion recovery) were made. Finally, T1-weighted spin-echo images were made in the coronal plane of the knee.

All of the magnetic resonance images were made with the knee in extension, with special attention paid to proper visualization of the patellofemoral joint, and the findings were analyzed and classified according to methods described in previous studies^28,32,38,48. The parameters that were evaluated included the thickness and signal intensity of the patellar cartilage and the roughness of the patellar surface. Each parameter was evaluated separately for the medial and lateral facets of the patella, and the findings were classified as normal or as indicating a mild, moderate, or severe abnormality.

In the evaluation of the thickness of the patellar cartilage, a mild abnormality indicated that the thickness was decreased by less than 25 percent compared with that on the contralateral side; a moderate abnormality, that it was decreased by 25 to 75 percent; and a severe abnormality, that there was more than 75 percent thinning, which extended to the level of the subchondral bone at some sites. In the evaluation of increased signal intensity of the patellar cartilage and increased roughness of the patellar surface, a mild abnormality indicated a small local change only (less than five millimeters of involvement); a moderate abnormality, a change in a more extended chondral area (six to ten millimeters of involvement); and a severe abnormality, involvement of the entire cartilage area of the medial or lateral facet of the patella.

Later on, and entirely separately from the evaluation that was just described, each finding on the magnetic resonance images of the affected knee was compared with that on the images of the contralateral knee, and if the finding was worse at the affected site the difference was recorded as an abnormality associated with the patellofemoral pain syndrome. Finally, each affected knee was given an overall classification of normal (no osteoarthritis), mildly affected (less than a 25 percent reduction in the thickness of the cartilage, alone or in combination with other abnormalities), moderately affected (a 25 to 75 percent reduction in the thickness of the cartilage, alone or in combination with other abnormalities), or severely affected (severe loss of cartilage, alone or in combination with other signs of patellofemoral osteoarthritis).

Standard anteroposterior and lateral weight-bearing radiographs, a tunnel radiograph, and a tangential radiograph of the patella with the knee in 30 degrees of flexion were made^22,23,33. The patellar radiographs, which are less sensitive than magnetic resonance images with regard to the detection of early degeneration of the cartilage but are definitely able to show advanced changes, were analyzed with regard to patellar osteophytes, subchondral sclerosis, subchondral cysts, and narrowing of the patellofemoral joint space. These parameters were recorded and were classified in the same manner as the findings on the magnetic resonance images were—that is, each knee was given an overall radiographic classification of normal or of mildly affected, moderately affected, or severely affected by osteoarthritis of the patellofemoral joint.

Bone Densitometry

At the seven-year follow-up evaluation, the bone-mineral density of the distal part of the femur, the patella, and the proximal part of the tibia was measured bilaterally, in grams per square centimeter, with use of our standardized measurement protocol for a dual-energy x-ray absorptiometric scanner (Norland XR-26; Norland, Fort Atkinson, Wisconsin)^39,40. The purpose of this examination was to determine whether the chronic patellofemoral pain syndrome had caused bone loss or osteopenia in the affected knee compared with the unaffected knee. As in our earlier studies of disuse osteopenia, a deficit in bone-mineral density of 5 percent or more at the affected site was considered clinically important^15,19.

Compliance by the Patients

As noted earlier, a total of fifty-three patients were initially enrolled in the study. Two patients (one in Group A and one in Group C) who had clear evidence of patellofemoral osteoarthritis were inadvertently randomized into the study; they were subsequently excluded from the trial. Another patient in Group C never returned to the clinic after the initial examination, and a patient in Group B had an intense, aseptic effusion (reactive synovitis) following the first injection (physiological saline solution) and the treatment was therefore discontinued¹⁸. This left a total of forty-nine patients in the study. There were no other complications, side effects, or noteworthy problems. The compliance of these forty-nine patients was excellent. All returned for follow-up visits until the time of the six-month evaluation, and all conscientiously followed the instructions for their treatment group and were well motivated according to the weekly reports to the attending physician¹⁸.

Forty-five (92 percent) of the forty-nine patients returned for the seven-year follow-up evaluation. The six-month results indicated that almost three-fourths of the patients had complete subjective, functional, and clinical recovery; with the numbers available, no significant or clinically important differences were detected among the three treatment groups¹⁸. Because analysis of the data also showed no differences among the groups at seven years, the data for the three groups were pooled and were analyzed together.

Statistical Analysis

Changes in the continuous outcome variables between the follow-up intervals (baseline [at the initial examination] compared with seven years and six months compared with seven years) were analyzed with use of the matched, paired t test. The same test was used for comparison of the bone-mineral-density measurements between the affected and unaffected knees. Changes in the categorical outcome variables between the six-month and seven-year assessments were analyzed with use of the McNemar test.

In each part of the analysis, an alpha level of less than 5 percent (p < 0.05) was considered significant. The given levels of significance were derived from two-tailed tests. The results are given as the mean and the standard deviation, with the 95 percent confidence interval.

Results

Introduction | Materials and Methods | Results | Discussion | References

Subjective Evaluation

The pain score, as recorded by the patients on the 100-millimeter visual-analog scale, improved significantly between the baseline and seven-year examinations (p < 0.001). Most of the improvement occurred between the baseline and six-month evaluations; the small additional improvement that occurred between six months and seven years could not be shown to be significant, with the numbers available (Fig. 1, A). Thirty (67 percent) of the forty-five patients reported that the overall status of the knee was excellent at six months compared with thirty-six patients (80 percent) at seven years (p = 0.18).

Eleven (24 percent) of the forty-five patients began to note qualitatively similar but milder symptoms in the initially asymptomatic, contralateral knee during the seven-year follow-up interval, thus confirming the concept that some patients may have symptoms of patellofemoral pain syndrome in both knees. The symptoms on the contralateral side occurred four years to three months before the seven-year follow-up evaluation and were present at the time of the follow-up evaluation in six of the eleven patients. The symptom-inducing activities were similar for the two knees.

Functional Evaluation

The scores according to the functional scales of Lysholm and Gillquist²⁷ and Tegner et al.⁴³ increased over time, as did the values for muscle strength (Fig. 1, B and C, and Fig. 2). The improvement in each of these outcome parameters was highly significant (baseline compared with seven years, p < 0.001 for the scores according to the scales of Lysholm and Gillquist²⁷ and Tegner et al.⁴³ and p = 0.001 for muscle strength). With the numbers available, no significant change was detected between six months and seven years.

All forty-five patients were symptomatic on each test of knee function at the time of the initial examination (Table I). Most patients (thirty-two [71 percent], thirty-five [78 percent], and thirty-nine [87 percent] for the three tests) were asymptomatic at six months, and we could detect no significant change between six months and seven years (Table I).

Thus, the good functional results that were noted at six months were maintained over time, and in most of the patients the disease did not progress to chronic disability.

Clinical Evaluation

At the time of the initial (baseline) examination, all forty-five patients had symptoms on the patellar compression and apprehension tests as well as crepitation on the compression test (Table II). At six months, the number of patients who had no symptoms or crepitation on these tests had clearly increased (Table II); however, the number of patients who had no symptoms on the patellar compression and apprehension tests had decreased by the time of the seven-year follow-up, from forty-two (93 percent) and forty (89 percent) to thirty (67 percent) and thirty-one (69 percent). These changes were significant (p = 0.002 and p = 0.023).

Although only nineteen patients (42 percent) had no crepitation on the patellar compression test at six months, this number decreased further over time, to nine patients (20 percent) at seven years (p = 0.021). The physician's overall assessment showed a similar trend, with thirty-four patients (76 percent) having complete recovery at six months compared with thirty (67 percent) at seven years; however, with the numbers available, this change was not found to be significant (p = 0.420) (Table II).

Thus, the results of the clinical evaluation were not as good as those of the subjective and functional evaluations, and they became worse over time. However, two-thirds of the patients still had complete recovery at seven years, as determined by the physician.

Findings on Magnetic Resonance Images and Radiographs

None of the patients had magnetic resonance imaging at the time of the baseline evaluation. Bilateral magnetic resonance images and radiographs of thirty-seven patients were available at seven years. These images showed no abnormalities in twenty-four patients (65 percent); mild abnormalities, such as a slight reduction in the thickness of the patellar cartilage, a slight increase in the signal intensity of the patellar cartilage, or slight roughness of the patellar surface, in four patients (11 percent); moderate abnormalities in seven patients (19 percent); and severe abnormalities (patellofemoral osteoarthritis) in two patients (5 percent).

The patellar radiographs showed no changes in thirty patients (81 percent); mild changes, such as small patellar osteophytes, mild subchondral sclerosis, or slight narrowing of the patellofemoral joint space, in six patients (16 percent); and severe changes (patellofemoral osteoarthritis) in one patient (3 percent).

Thus, in most of the patients the chronic patellofemoral pain syndrome did not progress to patellofemoral osteoarthritis during the seven-year follow-up interval.

Findings on Bone Densitometry

Bone-densitometry measurements in the distal part of the femur and the proximal part of the tibia were obtained for forty-two patients, and measurements in the patella were obtained for forty patients (Table III).

The mean deficit in the bone-mineral density of the affected knee compared with that of the unaffected knee was small but significant at every site that was measured. The deficit was 3.3 percent in the distal part of the femur, 2.5 percent in the patella, and 2.0 percent in the proximal part of the tibia (p = 0.001, 0.020, and 0.003, respectively).

Thus, the disease resulted in only a slight reduction in the bone-mineral density of the affected knee during the seven-year follow-up interval.

Discussion

Introduction | Materials and Methods | Results | Discussion | References

Our prospective seven-year follow-up of patients who had chronic patellofemoral pain syndrome showed that the good subjective and functional results that had been noted at six months were maintained over time (Table I and Figs. 1 and 2). Furthermore, in most of the patients, the condition did not lead to patellofemoral osteoarthritis or osteopenia, as determined with use of magnetic resonance imaging, radiography, and bone densitometry. However, the results of the seven-year clinical evaluation were not as good as those of the subjective and functional evaluations; significantly fewer patients were asymptomatic on the patellar compression and apprehension tests and had no patellar crepitation on the compression test at seven years than at six months (Table II). However, two-thirds of the patients had complete clinical recovery at seven years, as determined by the attending physician (Table II).

Thus, the long-term prognosis for patients who are managed nonoperatively for chronic patellofemoral pain syndrome appears to be good, and in most patients the condition does not result in chronic disability or radiographic abnormalities.

To our knowledge, this is the first prospective long-term follow-up study in which patients who had chronic patellofemoral pain syndrome were evaluated not only with subjective, functional, and clinical measures but also with a range of radiographic methods; however, our study had some limitations. The duration of follow-up of seven years from the commencement of treatment and rehabilitation (eight years from the onset of symptoms) is not sufficient to allow definitive conclusions. Despite the good subjective and functional outcomes, thirty-six (80 percent) of the forty-five patients still had characteristic patellofemoral crepitation on the patellar compression test, and the importance of this finding is not known. Only a duration of follow-up of ten to twenty years will provide a clear picture of the natural history of this disorder.

The reasons for the pain in chronic patellofemoral pain syndrome are not clear; however, the presence of mild osteopenia in the symptomatic knees at the seven-year follow-up evaluation suggests increased osseous metabolic activity or increased osteoclastic activity⁸. The increased osseous metabolic activity could have been detected with scintigraphic methods, and some investigators believe that osteopenia induced by patellofemoral pain syndrome is an indication of altered osseous homeostasis, which could be responsible for some of the pain reported by affected patients⁸.

There is no consensus regarding how to manage a patient who has chronic patellofemoral pain syndrome. Systematic rehabilitation of the quadriceps muscle has been emphasized by many authors^{4,6,9-13,20,21,25,29,31,45}. Bennett and Stauber reported major clinical improvement after a four-week regimen of quadriceps training three times a week³, and a similar finding was described recently by Thomeé⁴⁴. Our six-month results¹⁸ were consistent with these findings, and the current study demonstrates that the benefits were maintained over time.

In summary, this prospective follow-up study showed that the seven-year outcome for patients who had been managed nonoperatively for chronic patellofemoral pain syndrome was usually good, as determined by subjective, functional, and clinical assessments and by the findings on magnetic resonance images, radiographs, and bone densitometry. Almost two-thirds of the patients had full recovery at seven years, and only a few had chronic disability or patellofemoral osteoarthritis. An even longer duration of follow-up is needed to determine the natural history of chronic patellofemoral pain syndrome.

References

Introduction | Materials and Methods | Results | Discussion | References

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TABLE I NUMBER OF PATIENTS WHO WERE ASYMPTOMATIC ON FUNCTIONAL TESTS OF THE KNEE*

*The values are based on a total of forty-five patients. †According to the McNemar test.

Test	Baseline Evaluation	At 6 Mos.	At 7 Yrs.	P Value for Difference Between 6 Mos. and 7 Yrs.†
Hopping with affected limb	0	35 (78%)	34 (76%)	1.000
Duck-walking	0	39 (87%)	36 (80%)	0.380
25-repetition full-squat	0	32 (71%)	32 (71%)	1.000

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TABLE I NUMBER OF PATIENTS WHO WERE ASYMPTOMATIC ON FUNCTIONAL TESTS OF THE KNEE*

*The values are based on a total of forty-five patients. †According to the McNemar test.

Test	Baseline Evaluation	At 6 Mos.	At 7 Yrs.	P Value for Difference Between 6 Mos. and 7 Yrs.†
Hopping with affected limb	0	35 (78%)	34 (76%)	1.000
Duck-walking	0	39 (87%)	36 (80%)	0.380
25-repetition full-squat	0	32 (71%)	32 (71%)	1.000

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*The values are based on a total of forty-five patients. †According to the McNemar test.

	Baseline Evaluation	At 6 Mos.	At 7 Yrs.	P Value for Difference Between 6 Mos. and 7 Yrs.†
No symptoms on patellar tests
Compression	0	42 (93%)	30 (67%)	0.002
Apprehension	0	40 (89%)	31 (69%)	0.023
No crepitation on patellar compression test	0	19 (42%)	9 (20%)	0.021
Complete recovery as determined by physician	0	34 (76%)	30 (67%)	0.420

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*The values are based on a total of forty-five patients. †According to the McNemar test.

	Baseline Evaluation	At 6 Mos.	At 7 Yrs.	P Value for Difference Between 6 Mos. and 7 Yrs.†
No symptoms on patellar tests
Compression	0	42 (93%)	30 (67%)	0.002
Apprehension	0	40 (89%)	31 (69%)	0.023
No crepitation on patellar compression test	0	19 (42%)	9 (20%)	0.021
Complete recovery as determined by physician	0	34 (76%)	30 (67%)	0.420

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TABLE III RELATIVE DEFICITS IN BONE-MINERAL DENSITY (GRAMS PER SQUARE CENTIMETER) IN THE AFFECTED KNEE COMPARED WITH THE CONTRALATERAL, UNAFFECTED KNEE

Site*	Percent Difference† (Grams per Square Centimeter)	P Value‡
Distal part of femur (n = 42)	-3.3 ± 5.9 (-5.1 to -1.4)	0.001
Patella (n = 40)	-2.5 ± 6.7 (-4.7 to -0.4)	0.020
Proximal part of tibia (n = 42)	-2.0 ± 4.2 (-3.3 to -0.7)	0.003

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TABLE III RELATIVE DEFICITS IN BONE-MINERAL DENSITY (GRAMS PER SQUARE CENTIMETER) IN THE AFFECTED KNEE COMPARED WITH THE CONTRALATERAL, UNAFFECTED KNEE

Site*	Percent Difference† (Grams per Square Centimeter)	P Value‡
Distal part of femur (n = 42)	-3.3 ± 5.9 (-5.1 to -1.4)	0.001
Patella (n = 40)	-2.5 ± 6.7 (-4.7 to -0.4)	0.020
Proximal part of tibia (n = 42)	-2.0 ± 4.2 (-3.3 to -0.7)	0.003