Melorheostosis is often thought of as a benign sclerosing bone dysplasia, the aetiology of which remains uncertain. Lesions follow innervation of the spinal sensory nerves leading to the hypothesis by Murray and McCredie that embryonic infection of these nerves causes neural scarring and segmental bone sclerosis. Dermatomal involvement of the same sensory nerve root may be responsible for the associated cutaneous manifestations.12
Kim et al
demonstrated down regulation of adhesion proteins involved in osteoblastic regulation, specifically transforming growth factor ß induced gene product, which may contribute to the development of hyperostosis and associated soft tissue abnormalities.13
Endo et al
demonstrated increased collagen secretion from dermal fibroblasts overlying involved bone and suggested that cortical hyperostosis may influence proliferation of neighbouring deep dermal collagen to produce the overlying skin changes seen.14
On plain radiography, melorheostosis is classically described as periosteal hyperosteosis; however, a review of 23 cases by Freyschmidt found the most frequent appearance was an osteoma-like hyperosteosis on the endosteal surface of the bone. The lesions are typically eccentrically placed with no evidence of bony destruction.1
Isotope bone scanning reveals increased uptake in the same distribution seen on plain radiography reflecting an increase in bone metabolism.
Histology is non-specific but is useful to exclude malignancy as melorheostosis has been associated with a number of tumours, including osteogenic sarcoma. Extensive cortical sclerosis is usually seen with some areas of immature bone and active bone turnover. Small bone islands within the soft tissue have also been noted.1,2
Both periosteal and endosteal patterns of hyperosteosis were seen on plain radiography in our patient. Isotope bone scanning revealed increased uptake in the same distribution as the plain radiograph changes. Bone biopsy was performed to exclude the possibility of malignancy. It revealed changes consistent with benign bone dysplasia and small bone islands within the soft tissue consistent with melorheostosis.
Bisphosphonates are used for symptomatic control in both malignant and non-malignant diseases associated with increased bone turnover. They have been shown to decrease bone pain, slow progression of bone lesions and decrease the risk of pathological fracture.15,16
Nitrogen containing bisphosphonates inhibit osteoclast-mediated bone resportion by direct and indirect actions on osteoblasts and macrophages. Bisphosphonates also decrease bone vascularity and zoledronic acid has been shown in vitro
to be a potent inhibitor of angiogenesis.17
Potential causes of bone pain in melorheostosis include increased osteoclastic bone resorption and activation of pain receptors, raised intraosseous pressure and increased vascularity secondary to hyperosteosis and soft tissue involvement around joints. Thus, bisphosphonate treatment via a number of mechanisms would be expected to reduce inflammatory bone pain and symptoms in melorheostosis. Donath et al
described a case of melorheostosis with extensive bilateral disease and elevated alkaline phosphatase where the patient was treated with 30 mg of pamidronate daily for 6 days. This resulted in a rapid improvement in symptoms; however, alkaline phosphatase fell only slightly and the radionuclide bone scan appearance was unchanged.7
In this case the diagnosis of melorheostosis was made incidentally and the patient was not particularly symptomatic at initial diagnosis. Histology revealed little in the way of active bone turnover, which may have reflected the fact that the disease was relatively quiescent at that point. When the patient was referred to the Rheumatology Department in 2006 he was clearly symptomatic. Markers of bone turnover were within the normal reference range; however, only a relatively small amount of bone was affected by melorheostosis. Repeat isotope bone scan in 2006 demonstrated that the intense uptake along the right tibial shaft had encroached further on the proximal metaphysis, in keeping with an increase in disease activity.
A single infusion of 5 mg zoledronic acid given over 30 minutes resulted in a dramatic improvement in pain, temperature and size of the melorheostotic lesion and no further treatments have been required so far. Serum β cross-laps were significantly suppressed following treatment and have remained so. Zoledronic acid may decrease the frequency of disease activity as well as reducing symptoms during an active phase.
Recent guidance has been issued regarding osteonecrosis of the jaw (ONJ) and bisphosphonate treatment by the American Society for Bone and Mineral Research (ASBMR). It is recognised that ONJ is commoner, although still very rare, with intravenous compared to oral bisphosphonate treatment. It is very important to ensure patients do not require any dental extractions and have been seen recently by a dental practitioner prior to receiving intravenous bisphosphonate treatment.18
This is the first reported case of the successful use of zoledronic acid in the symptomatic treatment of melorheostosis and demonstrates the value of monitoring with a bone resorption marker.
- Melorheostosis is a rare disorder characterised by mesodermal dysplasia of the bone.
- Symptoms include pain, oedema and limitation of joint movement. Treatment options have to date been limited.
- We report prolonged symptomatic benefit after a single infusion of 5 mg zoledronic acid accompanied by long-term suppression of the bone resorption marker β cross-laps.
- It is important to ensure good dental hygiene and adequate 25-hydroxy vitamin D levels prior to administering intravenous bisphosphonates due to the increased risk of osteonecrosis of the jaw.
- We suggest that melorheostosis can be treated with intravenous zoledronic acid and that treatment can be monitored by the use of a specific bone resorption marker.