In this Journal feature, information about a real patient is presented in stages (boldface type) to an expert clinician, who responds to the information, sharing his or her reasoning with the reader (regular type). The authors' commentary follows.

A 31-year-old man presented to the emergency department with pain in the left shoulder.

He had tripped over the shoulder strap of his backpack earlier in the day and noted immediate severe pain around his left shoulder, without paresthesias or neck pain.

Physical examination revealed bony point tenderness over the humeral head and limited range of motion due to pain; crepitus was present. Shoulder radiographs revealed an impacted fracture of the left humerus and evidence of osteopenia (Figure 1).

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  Figure 1. Radiograph of the Left Shoulder.

The impacted humeral fracture (large arrow) and osteopenia (small arrow) are shown. 

This man had a traumatic fracture of his left humerus and was noted to have radiographic evidence of osteopenia.

Plain radiographs are not sensitive for bone loss; the fact that osteopenia was detected on such imaging suggests considerable bone loss, and a formal assessment of bone mineral density (e.g., by means of dual-energy x-ray absorptiometry) is warranted.

When osteopenia is suspected in a male patient who is younger than 50 years, a careful history taking is essential.

The key components should include questions about fractures and the circumstances in which they occurred, growth and pubertal development in childhood, medication use, a thorough review of systems to screen for systemic diseases (particularly endocrinologic, gastrointestinal, hematologic, renal, and genetic diseases that might disrupt bone homeostasis or formation), and a family history of fractures or systemic diseases.

The patient reported normal pubertal development but was underweight as a child, with difficulty gaining weight. He had remained thin in adulthood until 2 years previously, when he unintentionally gained 20 lb (9 kg), which he maintained.

There were no changes in his diet or exercise pattern. He reported chronic fatigue, general weakness, diminished libido, and easy bruising. No diarrhea, oral ulcers, arthralgias, or rashes were reported.

He did not engage in excessive exercise or contact sports or have a history suggestive of an eating disorder.

His medical history was notable for multiple fractures of the femur, elbow, and wrist, without previous evaluation.

Additional history included pericarditis, erectile dysfunction, perforated tympanic membranes, hypertension, retinal tears with partial early detachments, myopia, kyphoscoliosis, â-thalassemia trait, and esophageal reflux.

The patient was a university graduate student. He took no medications. He smoked 10 cigarettes per day and did not use ethanol or illicit drugs.

There was no history of fractures in his mother, father, or 36-year-old brother.

His mother had hypothyroidism and fibromyalgia, and his father had melanoma and benign prostatic hypertrophy.

The history of fractures should prompt a detailed assessment of known or occult causes of trauma, such as abuse, as well as initiation of a metabolic and genetic evaluation.

If the diagnosis of severe osteopenia or osteoporosis is established by means of dual-energy x-ray absorptiometry, evaluation is warranted for secondary causes of bone loss.

On physical examination, one should look for signs of systemic diseases. Blue sclerae are suggestive, but not pathognomonic, signs of osteogenesis imperfecta. Moon facies, central obesity, and wide purple striae are suggestive of hypercortisolism.

On physical examination, the patient appeared to be in mild discomfort from his fracture. His height was 175 cm, weight 76 kg, and body-mass index (the weight in kilograms divided by the square of the height in meters) 24.9. His blood pressure was 134/98 mm Hg, and his pulse 86 beats per minute and regular.

• He did not have moon facies or scleral discoloration.
• The pupils were equal and reactive to light.
• The oropharynx and teeth appeared normal.
• There was no lymphadenopathy in the cervical, axillary, or inguinal areas.
• The thyroid was normal in size and without nodules.
• The lung fields were clear on auscultation.

No gynecomastia was present. Cardiac examination revealed a nondisplaced point of maximal impulse, regular rate and rhythm, and no murmurs, rubs, or gallops.

Back examination revealed kyphosis and scoliosis of the thoracic spine. Multiple areas of tenderness were palpated over the posterior left ribs.

The abdomen was soft and nontender, with normal bowel sounds and no hepatosplenomegaly or masses. The bilateral testicular volume was normal. The skin was pale, with multiple nevi as well as ecchymoses over the left shoulder. No striae or rashes were observed.

Examination of the shoulder was limited by the patient's pain, but the nerves and vascular structures of the left arm appeared to be intact.

Reflexes were normal, and there was no proximal-muscle weakness or joint laxity or hypermobility.

The physical examination shows no obvious signs of endocrinologic or genetic disorders. However, the patient does have evidence of kyphoscoliosis, suggesting possible past vertebral compression fractures.

Furthermore, the pain over his thoracic ribs could indicate additional fractures from his recent trauma or past rib fractures that have healed incompletely.

The initial laboratory evaluation should include an assessment for secondary causes of bone loss in young men, with tests of thyroid, parathyroid, renal, and gonadal function, as well as vitamin D levels.

The white-cell count was 7710 per cubic millimeter, hematocrit was 41.5% with a mean corpuscular volume of 60 µm³, and platelet count was 233,000 per cubic millimeter.

The level of blood urea nitrogen was 15 mg per deciliter (5.4 mmol per liter), creatinine 1.1 mg per deciliter (97 µmol per liter), calcium 8.8 mg per deciliter (2.2 mmol per liter), albumin 4.5 g per deciliter, and phosphate 3.6 mg per deciliter (1.2 mmol per liter).

Electrolytes and liver-function results were normal except for a slight elevation in the aspartate aminotransferase level, at 53 U per liter (normal range, 7 to 52).

Total protein and thyrotropin levels were normal.

The 25-hydroxyvitamin D level was 35 ng per milliliter (87 nmol per liter) (normal range, 25 to 80 ng per milliliter [62 to 200 nmol per liter]), and the parathyroid hormone level was 56 pg per milliliter (normal range, 11 to 80).

The morning cortisol level was 11.7 µg per deciliter (322.8 nmol per liter). A urinalysis was normal.

A morning total testosterone level was 1569 pg per milliliter (5440 pmol per liter) (normal range, 2220 to 6650 pg per milliliter [7697 to 23,056 pmol per liter]).

The level of luteinizing hormone was 3.2 mU per milliliter (normal range, 1.7 to 8.6), and the follicle-stimulating hormone level was 1.7 mIU per milliliter (normal range, 3.1 to 12.2).

The patient had an uncomplicated open reduction and internal fixation of the left humeral head. Morphine and oxycodone were prescribed for pain control.

Bone fragments resected during surgery were evaluated for metabolic bone disease with the use of static histomorphometry.

The bone marrow contained fat necrosis, reactive-appearing spindle cells, and granulation tissue, findings that were consistent with reactive changes. No clear diagnosis could be made on the basis of these findings.

Dual-energy x-ray absorptiometry, performed after surgery, showed T scores of –4.4 in the spine, –2.7 in the hip, and –3.1 in the neck of the femur.

This patient's dual-energy x-ray absorptiometry scan shows osteoporosis (i.e., a T score >2.5 SD below the mean for a sex-matched healthy young adult).

The severity of the patient's osteoporosis, early age at diagnosis, and extensive history of fractures point to a secondary cause.

A notable laboratory abnormality is the low level of total testosterone, with the normal level of luteinizing hormone and the subnormal level of follicle-stimulating hormone, which are not consistent with the low level of testosterone.

These findings are suggestive of central hypogonadism, which could explain the osteoporosis as well as the patient's symptoms of erectile dysfunction, low libido, and fatigue.

However, this single testosterone value has not been confirmed, and levels may be temporarily suppressed owing to acute stress, the use of narcotic analgesic drugs, or the time of day when the sample was drawn (since testosterone levels vary diurnally and peak in the morning).

In addition, most testosterone is bound to albumin and sex hormone–binding globulin; thus, conditions that affect levels of albumin or sex hormone–binding globulin also can influence testosterone levels.

Repeat measurement of a morning total testosterone level is warranted before concluding that the patient has hypogonadism.

In addition to the diagnoses mentioned above, other underlying systemic conditions should be considered as possible causes of the patient's bone loss.

• Celiac disease is possible, given his history of being underweight, although he had no diarrhea or rash, and his vitamin D levels were normal.
• Alcoholism is another potential cause, but he reported that he did not consume ethanol, and it is unusual for ethanol overuse to cause severe bone loss at his young age.
• Cushing's syndrome is unlikely because of the normal proximal-muscle strength and the absence of other signs of cortisol excess.
• Multiple myeloma is extremely rare at this patient's age and is unlikely given his normal level of total serum protein.
• Other rare conditions to be considered include mastocytosis and hypercalciuria.
• Radiographic assessment for abnormal bone mineralization, pathologic fractures (or impending fractures), and lytic bone lesions should be performed as well.
• A repeat outpatient measurement of the morning testosterone level was normal, at 3356 pg per milliliter (11,635 pmol per liter).
• An overnight dexamethasone suppression test and 24-hour urinary calcium and 1,25-dihydroxyvitamin D levels were normal.
• Results of serum and urinary protein electrophoresis and the insulin-like growth factor 1 (somatomedin C) level were normal. Tests for endomysial and tissue transglutaminase antibodies were negative.
• The tryptase level was normal. A skeletal survey showed multiple compression fractures of the thoracic spine without any lytic lesions (Figure 2).
• The patient was treated with risedronate at a dose of 35 mg weekly, calcium carbonate at a dose of 600 mg twice daily, and vitamin D₂ at a dose of 50,000 IU weekly for 6 weeks, followed by a combination of calcium (500 mg) and vitamin D₃ (200 IU) twice daily.

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  Figure 2. Radiograph of the Thoracic Spine.

The arrows point to compression fractures.

SEE FULLTEXT

NEJM Volume 361:74-79 July 2, 2009 Number 1

Asaf Bitton, M.D., Maria Yialamas, M.D., Bruce D. Levy, M.D., Joel T. Katz, M.D., and Joseph Loscalzo, M.D., Ph.D.

http://content.nejm.org/cgi/content/full/361/1/74

http://www.e-medicum.com/noticiasDelDia/verNoticia.php?noticia=82888