Methotrexate Osteopathy in a Patient with Rheumatoid Arthritis

Methotrexate Osteopathy in a Patient with Rheumatoid Arthritis

OLGU SUNUMU
Methotrexate Osteopathy in a
Patient with Rheumatoid Arthritis:
Case Report
Tuba YILDIRIM GÜNAY,a
Yeşim GARİP,b
Hatice BODURc
a
Clinic of Physical Medicine and
Rehabilitation,
İskenderun State Hospital, Hatay,
b
Clinic of Physical Medicine and
Rehabilitation
Private Başak Medical Center,
c
Clinic of Physical Medicine and
Rehabilitation
Ankara Numune Training and
Research Hospital, Ankara
Geliş Tarihi/Received: 06.05.2014
Kabul Tarihi/Accepted: 19.08.2014
This abstract was presented at Congress of
Excellence in Rheumatology
(25-28 Ocak 2012, İspanya- Madrid)’.
[Gunay T, Garip Y, Bodur H, ‘‘Methotrexate
osteopathy in a patient with
rheumatoid arthritis’’, Excellence in
Rheumatology, Rheumatology (Oxford)
volume 51 supplement 2 January 2012, ii5
(PP33), Madrid, 25-28 January 2012]
Yazışma Adresi/Correspondence:
Yeşim GARİP
Private Başak Medical Center,
Clinic of Physical Medicine and
Rehabilitation, Ankara,
TÜRKİYE/TURKEY
[email protected]
ABSTRACT Methotrexate (MTX) is an anti-metabolite frequently used in the treatment of autoimmune conditions such as rheumatoid arthritis (RA) and psoriatic arthritis. Long-term use of
MTX is associated with various potential side effects. In rare circumstances, it may lead to osteopathy, which is characterized by bone pain, osteoporosis and fractures. Herein, a 69-year-old
woman female patient who was receiving low dose MTX for RA and admitted to our outpatient
clinic with complaints of swelling of the right leg and ankle and metatarsalgia aggravated with
weight-bearing is presented. In physical examination of the patient, right ankle, fourth and fifth
metatarsophalangeal joints were swollen, painful and tender to palpation. Laboratory parameters including complete blood count, erythrocyte sedimentation rate, c-reactive protein, serum total calcium, phosphorus, 25-hydroxy vitamin D3, parathyroid hormone, alkaline phosphatase were in
normal ranges. In radiographic examination, fifth metatarsal fracture was observed. This finding was
confirmed with computed tomography. The bone mineral density (BMD) results, measured by dual
energy x-ray absorptiometry, were as follows; lumbar spine BMD T-score: -2.2, femoral neck BMD
T-score: -2.2. The patient was diagnosed with MTX osteopathy due to long-term MTX therapy.
Symptoms were resolved when MTX was discontinued. In case of joint pain and swelling, inconsistent with disease activity in patients who are on long-term MTX therapy, osteopathy, which is
characterized with a triad of bone pain, osteoporosis and fractures should be kept in mind.
Key Words: Rheumatoid arthritis; methotrexate (MTX)
ÖZET Metotreksat (MTX), romatoid artrit (RA) ve psöriyatik artrit gibi otoimmün hastalıkların tedavisinde sıklıkla kullanılan bir anti-metabolittir. Uzun dönem MTX kullanımı bir çok potansiyel yan etkiyle ilişkilidir. Nadir durumlarda kemik ağrısı, osteoporoz ve kırıklarla karakterize olan osteopatiye yol
açabilir. Burada, RA tanısı ile MTX tedavisi alan ve sağ bacakta ve ayak bileğinde şişlik ve yüklenme
ile artan metatarsalji şikayetleri ile polikliniğimize başvuran 69 yaşında bir kadın hasta sunulmuştur.
Hastanın fiziksel muayenesinde, sağ ayak bileği, dördüncü ve beşinci metatatarsofalangeal eklemler
şiş, ağrılı ve palpasyonla hassastı. Tam kan sayımı, eritrosit sedimentasyon hızı, c-reaktif protein, serum
total kalsiyum, fosfor, 25-hidroksi vitamin D3, paratiroid hormon, alkalen fosfataz değerleri normal
sınırlardaydı. Radyografik incelemede 5. metatarsal kırığı gözlendi. Bu bulgu, bilgisayarlı tomografi ile
doğrulandı. Dual enerji x-ışını absorbsiyometrisi ile ölçülen kemik mineral dansitesi (KMD) sonuçları;
lomber omurga KMD T-skoru: -2,2, femur boyun KMD T-skoru: -2,2 idi. Hastaya uzun dönem MTX
tedavisine bağlı MTX osteopatisi tanısı kondu. Semptomlar MTX kesildiği zaman geriledi. Hastalık aktivitesi ile uyumlu olmayan eklem ağrısı ve eklem şişliği varlığında, uzun süreli MTX tedavisi alanlarda, ayırıcı tanıda, kemik ağrısı, osteoporoz ve kırık triadı ile karakterize osteopati akılda tutulmalıdır.
Anahtar Kelimeler: Romatoid artrit; metotreksat (MTX)
M
Romatol Tıp Rehab 2014;25(2):42-4
Copyright © 2014 by
Türk Tıbbi Rehabilitasyon Kurumu Derneği
42
TX is a structural analogue of folic acid, which is commonly used
in high doses for the treatment of malignancies, and in lower
doses over prolonged periods for the treatment of RA and various
Romatol Tıp Rehab 2014;25(2)
METHOTREXATE OSTEOPATHY IN A PATIENT WITH RHEUMATOID ARTHRITIS: CASE REPORT
inflammatory diseases. It may lead to osteopathy
which is characterized by a triad of bone pain, osteoporosis and insufficiency fractures.1 Herein we
report a patient who was receiving MTX for RA
presenting with metatarsal stress fracture.
CASE REPORT
A 69-year-old woman with rheumatoid arthritis on
long-term MTX therapy was referred to our outpatient clinic with swelling of the right leg and ankle
and metatarsalgia aggravated with weight-bearing.
Her complaints had persisted for 15 days. In her
past medical history, she had been diagnosed with
RA for 15 years and received MTX up to 20
mg/week for the past 12 years. She had been
treated with prednisolone 7.5 mg daily for a year
in the beginning of her disease, but prednisolone
had been discontinued because of gastrointestinal
side effects. She had no history of trauma or osteoporotic or insufficiency fractures. She was postmenopausal and non-smoker.
Tuba YILDIRIM GÜNAY et al.
lowing: erythrocyte sedimentation rate (ESR) 20
mm/h (normal range: 0-20 mm/h), C-reactive protein (CRP) 1.5 mg/L (normal range: 0,00-5.00 mg/L),
serum total calcium 9.3 mg/dL (normal range: 8.510.6 mg/dL), serum ionized calcium 4.5 (normal
range: 4.5-5.2mg/dL), serum phosphorus 4.7 mg/dL
(normal range: 2.4-4.7 mg/dL), 25-hydroxy vitamin
D3 32.2 ng/ml (6.3-46.4 ng/ml), parathyroid hormone (PTH) 6 pmol/L (normal range:1.3-9.3 pmol/L
), alkaline phosphatase 72 u/L (normal range: 32-91
u/L). Thyroid function tests were normal.
Radiographs performed eight months later revealed an old fifth metatarsal fracture (Figure 1 and
2). This was confirmed with computed tomography
(CT). CT findings included the following: soft-tissue swelling, old fracture of the fifth metatarsal
bone with plantar displacement of the fracture fragment and periosteal reaction. The bone mineral
density results measured by dual energy x-ray absorptiometry were as follows; lumbar spine BMD Tscore: -2.2, femoral neck BMD T-score: -2.2.
In physical examination, the range of motion
of her ankle was normal. Right ankle, fourth and
fifth metatarsophalangeal joints were swollen,
painful and tender to palpation. Disease Activity
Score- 28 (DAS28) was 3.36 (moderate disease activity). Radiographs of right ankle and foot were
normal, showed no evidence of stress fracture.
She was diagnosed with MTX osteopathy due
to long-term MTX therapy. Bone pain was resolved
when MTX was discontinued, but the tenderness
of right ankle and fifth metatarsal persisted for
about one month.
Complete blood count and serum biochemistry
was normal. Laboratory parameters showed the fol-
MTX osteopathy is rare and its diagnosis is based
on characteristic clinical and radiographic features.
FIGURE 1: Anteroposterior view of right foot showing 5th metatarsal fracture.
FIGURE 2: Lateral view of right foot.
Romatol Tıp Rehab 2014;25(2)
DISCUSSION
43
Tuba YILDIRIM GÜNAY et al.
METHOTREXATE OSTEOPATHY IN A PATIENT WITH RHEUMATOID ARTHRITIS: CASE REPORT
It is characterized by severe lower extremity pain
and by osteoporosis particularly involving the
lower extremities. Radiographs usually show osteoporosis, fractures and thick dense provisional
zones of calcification and growth arrest lines resembling scurvy. Calcium phosphorus metabolism
is mostly within the normal ranges. When MTX is
discontinued, the fractures usually heal.1,2
It was first reported in children with childhood leukemia treated with high-dose MTX in
1970 by Ragab et al.3 Similarly, O’Regan S and
Stanisavljevic reported osteopathy due to high-dose
MTX in children with leukaemia.4,5
Similar clinical features were reported in patients with inflammatory arthritis on low-dose MTX
therapy.6-10 Preston reported a 58 year old woman
with stress fracture while receiving low weekly
doses of MTX.6 Initial radiographs of ankles showed
a sclerosis area at the distal left metaphysis. Radi-
1.
2.
3.
4.
5.
44
Koller A, Fill H, Kurz R, Riccabona G, Haas H.
Osteopathy due to methotrexate. Osterr Z
Onkol 1976;3(3):63-9.
Schwartz AM, Leonidas JC. Methotrexate osteopathy. Skeletal Radiol 1984;11(1):13-6.
Ragab AH, Frech RS, Vietti TJ. Osteoporotic
fractures secondary to methotrexate therapy
of acute leukaemia in remission. Cancer
1970;25(3):580-5.
O'Regan S, Melhorn DK, Newman AJ.
Methotrexate induced bone pain in childhood
leukaemia. Am J Dis Child 1973;126(4):48990.
Stanisavljevic S, Babcock A L. Fractures in
children treated with methotrexate for
ographs performed six months later showed bilateral distal tibial fractures and a proximal left tibial
fracture. Similarly in our case, initial radiographs
were normal. Radiographs performed eight months
later demonstrated fifth metatarsal fracture.
Mechanism of impaired bone formation during low dose MTX therapy is not very well known.
The results of metabolic studies showed an increased bone resorption in patients receiving
MTX.11 On the other hand, Uehara reported that
MTX suppressed bone formation by inhibiting differentiation of early osteoblastic cells.12
In conclusion, it is important that physician
should be aware of this complication in patients receiving MTX, because symptoms may easily be
confused with synovitis. Long term therapy with
MTX could be an extra risk factor for fractures in
RA patients receiving corticosteroids and in elderly
patients with senile osteoporosis.
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