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Mastocytosis comprises a heterogeneous group of disorders of mast cell proliferation. Infiltration of multiple organs by mast cells may occur, including skin and bone, with cutaneous and systemic variants being well described. There are few reports of the treatment of osteoporosis, a secondary manifestation of systemic mastocytosis (SM).1–3 We undertook a retrospective analysis of six patients with osteoporosis associated with SM treated with bisphosphonates.
The mean age of the patients was 58 years (range 40–70) and the mean duration of SM was 8 years (range 3–13). All patients had a past history of urticaria pigmentosa and had presented to their general practitioner with back pain. Four patients had vertebral crush fractures on plain radiography. Isotope bone scans in the remaining two patients showed diffuse skeletal uptake consistent with marrow infiltration. Bone marrow biopsy in all patients confirmed mast cell infiltration. All patients had mast cell mediator related symptoms (flushing, wheezing, diarrhoea with abdominal pain, pruritus, bone pain) and raised total serum tryptase levels persistently >20 ng/ml. This fulfilled the diagnostic criteria for SM, defined by multifocal histological lesions in the bone marrow or other extracutaneous organs (major criteria) together with cytological and biochemical signs (minor criteria) of systemic disease.4 Tryptase levels correlate with the clinical severity of SM,5 and we used this to monitor disease activity.
Treatment was started with bisphosphonates (annual intravenous pamidronate followed by alendronate in five patients, alendronate only in the sixth patient). No further fractures developed despite absence of specific treatment for mast cell proliferation. All patients had a subjective improvement in pain after bisphosphonate treatment. Hologic bone mineral density (BMD) measurements were assessed at baseline and at 1–2 yearly intervals thereafter. BMD in the lumbar spine rose in all patients from baseline; two patients (Nos 1 and 2) were excluded owing to multiple lumbar vertebral fractures. Total hip BMD rose in three patients and stabilised in the other three (table 1).
Disorders of mast cells, derived from the multipotent haematopoietic stem cell are rare. Cutaneous mastocytosis without systemic involvement manifests in childhood as urticaria pigmentosa and spontaneous regression occurs during puberty. Symptoms of SM are related to the release of mast cell mediators, including histamine, prostaglandins, leucotrienes, and proteases, with bone pain occurring frequently. The radiological findings in SM include diffuse osteoporosis with vertebral fractures and/or a combination of osteosclerotic and osteolytic lesions, primarily affecting the axial skeleton and ends of long bones. Solitary lesions (mastocytomas) may cause localised pain.
The cellular and pathophysiological mechanisms leading to osteoporosis in SM are poorly understood. Mast cells infiltrating bone marrow may have an inhibitory effect on the coupling of bone formation and resorption, with the balance in favour of the latter. It is unlikely that bone resorption is caused directly by mast cell release of heparin, prostaglandin D2, and tryptase.1,6
SM has been reported to account for a greater than expected cause of osteoporosis in the younger population.7 Indeed, back pain secondary to osteoporotic vertebral fractures may be the major presenting symptom of SM. BMD stabilised without the occurrence of further fractures in our patients. Fracture reduction is due not only to inhibition of osteoclasts by bisphosphonates but their ability to reduce the activation frequency and birth rates of new bone remodelling units and to enhance osteon mineralisation.8 Musculoskeletal pain in mastocytosis may be present in up to 28% of patients and is difficult to manage.9 Interestingly, our patients reported improvement in bone pain after bisphosphonate treatment.
In conclusion, SM, although rare, should be included in the differential diagnosis of idiopathic osteoporosis because of its significant morbidity. Bisphosphonates are effective in SM for osteoporosis and have a role in the associated refractory bone pain.