Case presentation
An 80-year-old gentleman independent from home presented to hospital on
the 18th April 2023 with a one-week history of acute
onset, progressively worsening large joint arthralgia and
musculoskeletal pain following his first dose of denosumab. This 60 mg
subcutaneous injection was prescribed by his general practitioner for
osteoporosis. He was previously well with no prior arthralgia or
musculoskeletal pain, infective symptoms, or history of falls or trauma.
There was no immediate reaction. However, approximately five hours after
denosumab administration, he began developing arthralgia and cramping
musculoskeletal pain of fluctuating severity, with involvement of his
bilateral knees, hips, thighs and shoulders. His symptoms were severe
enough to limit range of motion and function of affected joints and did
not respond to self-administered paracetamol and codeine treatment. The
symptoms progressively worsened over the course of one week, at which
point he also developed pain in his left wrist, which prompted him to
seek medical attention.
On presentation, he had persistent bilateral joint pain involving the
shoulders, knees and left wrist. He also had persistent musculoskeletal
pain involving the right arm and bilateral thighs. Arthralgia, pain and
joint stiffness were noted to be worse in the morning and eased through
the day. He did not have any localising infective symptoms, fevers or
constitutional symptoms apart from some fatigue associated with the
arthralgia and musculoskeletal pain. He did not have any temporal
headaches, visual disturbance or jaw claudication. He did not have
significant small joint arthralgia, sicca symptoms, ocular inflammation,
abnormal rash or symptoms of mononeuritis multiplex.
His medical history included osteoarthritis with a left total knee
replacement three years prior, and a right reverse shoulder joint
replacement ten years ago following a rotator cuff injury. He had
chronic obstructive pulmonary disease, hypothyroidism, ischaemic heart
disease and heart failure with reduced ejection fraction, all of which
were stable. He also had a T7 spinal compression fracture diagnosed five
months prior, with a dual x-ray absorptiometry (DEXA) scan confirming
osteoporosis.
His regular medications included aspirin 100 mg once daily, rosuvastatin
20 mg at night, sacubitril 24.3 mg + valsartan 25.7 mg twice daily,
furosemide 40 mg once daily, levothyroxine 100 µg once daily, nebivolol
5 mg once daily and spironolactone 12.5 mg once daily. He did not start
any of these medications recently. He did not have any drug allergies.
The patient was a retired salesman who lived at home with his wife and
was previously fully independent with his activities of daily living and
mobility–regularly walking unaided for several kilometres a day. He
ceased smoking 20 years ago following a 30 pack-year history, and did
not drink alcohol.
On examination, he was alert, orientated and comfortable at rest.
Observations were within normal limits and he was afebrile. He had an
average build. He had marked limitation of right shoulder abduction and
range of motion to less than 30 degrees along with generalised
tenderness on palpation of his shoulder girdle and deltoid muscle belly.
There were no bony step deformities nor focal areas of particular
tenderness. His left shoulder had similar tenderness but preserved range
of motion. He had tenderness on palpation of his left wrist but no
deforming polyarthropathy and no active tenosynovitis. There were no
stigmata of scleroderma, endocarditis or dermatomyositis. He had
limitation of hip flexion to less than 30 degrees bilaterally, along
with palpation tenderness in his quadriceps. He had preserved range of
motion in his knees without significant pain on anterior joint space
palpation. His power and sensation was preserved in all limbs. His gait
was slow and antalgic, but otherwise normal. He did not have significant
spinal tenderness or limited range of motion. He had no rash or evidence
of ocular inflammation. Cardiorespiratory and abdominal examination was
unremarkable and he was clinically euvolaemic.
Investigations on presentation revealed elevated inflammatory markers
with an erythrocyte sedimentation rate (ESR) of 140 mm/hr and C-reactive
protein (CRP) of 163.8 mg/L (Table 1). CRP peaked at 235.2 mg/L on the
following day. Ferritin was mildly elevated along with low transferrin
saturation, in keeping with an inflammatory state.
He had a mild normocytic anaemia with a normal platelet count (Table 1).
There was a mild monocytosis but otherwise normal white blood cell count
and differential. Renal function, liver function and thyroid function
tests were normal. There was mild hypocalcaemia with a corrected calcium
of 2.08 mmol/L, and low-normal phosphate of 0.76 mmol/L in the setting
of denosumab therapy. Parathyroid hormone was appropriately elevated.
25-hydroxy Vitamin D level was normal. Other serum electrolytes were
unremarkable. Creatine kinase was normal at 108 U/L.
Autoimmune serology revealed an elevated rheumatoid factor (RF) and
anti-cyclic citrullinated peptide antibodies (ACPA) (Table 1).
Antinuclear antibodies were detected at a 1:320 titre with a homogenous
and speckled pattern, but extractable nuclear antigen antibody screen
and double-stranded DNA antibodies were negative. Complement factor 3
and 4 levels were normal.
Respiratory virus swab was negative for Influenza A/B, Adenovirus,
Rhinovirus, Respiratory syncytial virus, Human parainfluenza virus 1-4
and Severe acute respiratory syndrome coronavirus 2 (SAR-CoV-2). Blood
and urine cultures were negative. Chest x-ray revealed expected
emphysematous changes, but no consolidation or pleural effusions.
Cervical spine x-ray revealed stable multilevel degenerative changes
without fracture or malalignment. Bilateral shoulder x-ray revealed a
previous right total shoulder replacement and narrowing of the left
glenohumeral joint space inferiorly, but no fracture or heterotopic soft
tissue ossification. Computerised tomography of the right shoulder did
not show any evidence hardware migration, periprosthetic fracture or
joint effusion. Ultrasound of the right shoulder revealed a
supraspinatus tendon anterior portion partial-thickness tear (Figure
1a), and subscapularis insertional tendinosis with a partial thickness
tear (Figure 1b). There was no significant subdeltoid subacromial
bursitis (Figure 1c). Long head of biceps was surgically absent
following shoulder replacement (Figure 1d).