We describe a patient who had hypophosphatemic rickets who was bedridden by her disease because of severe weakness and generalized bony aches. At the time of her presentation she was not on any medications and was started on calcitriol and started showing improvement in her muscle power. The patient was found to have severe osteoporosis so denosumab was added 2 months later, the condition of the patient continued to improve. Her phosphorous level started to improve approximately 7 months after treatment which is probably the major factor in the improvement of her muscle weakness.
Denusumab is a human immunoglobulin G2 monoclonal antibody that inhibits bone resorption by targeting RANKL, which is involved in osteoclast differentiation. It has been used successfully to treat osteoporosis, lytic lesions associated with bony metastasis and diseases with osteoclast overactivity, including giant cell tumors of the bone. It has been used off label to treat other diseases of the bone with similar osteoclastic pathology including central giant cell granuloma, aneurysmal bone cysts and fibrous dysplasia [
5]. The condition of the patient improved markedly on the medication. The patient did not develop any side effects from the denosumab such as hypocalcemia most likely due to the associated primary hyperparathyroidism in this patient. On reviewing the literature there were no cases reported on using denosumab for hypophosphatemic rickets but is has been used in a case of hypophosphatemic osteomalacia which was drug induced [
6] it also has been reported to be used in cases of osteogenesis imperfecta [
7]. Denosumab, in addition to other drugs are currently being investigated in phase III trials for use in hypophosphatemic rickets, hypophosphatasia and fibrodysplasia ossificans progressiva [
8]. Our patient had hyperparathyroidism which is one of the complications when treating such patients with calcitriol and phosphate supplements [
2,
3]. The level of alkaline phosphatase and parathyroid hormone levels although still high were decreasing over time. Calcitriol was discontinued at this time due to a high Vitamin D level and the recent increase in the calcium level. Nephrocalcinosis has been reported to occur in 34% of cases and tertiary hyperparathyroidism in 6% of patients in one study [
3]. It is mostly reported to occur secondary to prolonged treatment with phosphate [
9,
10]. We are not aware that our patient ever received phosphate salts in the past. Most likely our patient has primary hyperparathyroidism in addition to hypophosphatemic rickets. There has been a case reported to have hypophosphatemic rickets and primary hyperparathyroidism due to a de novo transloction with a breakpoint adjacent to α-Klotho, which encodes a β-glucoronidase, and is implemented in aging and regulation of FGF signaling [
11]. We will continue to treat her with denosumab and if her calcium remains high she may need cinalcacet or parathyroidectomy.