Protective Effect of Denosumab on Bone in Older Women with Primary Hyperparathyroidism

Eller-Vainicher, Cristina; Palmieri, Serena; Cairoli, Elisa; Goggi, Giovanni; Scillitani, Alfredo; Arosio, Maura; Falchetti, Alberto; Chiodini, Iacopo

doi:10.1111/jgs.15250

Cited by 55 publications

(26 citation statements)

References 35 publications

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“…Munro, et al reported that treatment of PHPT patients with cinacalcet for up to 5.5 years had no significant effect on the BMD [17]. In contrast, it has been reported that denosumab or bisphosphonate therapy can increase the BMD of osteoporotic patients with PHPT [18][19][20][21][22]. In another observational study in PHPT patients however, bisphosphonate therapy showed an association with an increased fracture risk as opposed to parathyroidectomy, which was found to be associated with a decreased fracture risk [23].…”

Section: Discussionmentioning

confidence: 98%

Effectiveness and safety of cinacalcet for primary hyperparathyroidism: a single center experience

et al. 2019

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Primary hyperparathyroidism (PHPT) is a common endocrine disease. Although surgical treatment is curative in most cases, there are few alternative therapies for the hypercalcemia caused by PHPT. Cinacalcet is a positive allosteric modulator of the calcium sensing receptor and was conditionally approved in Japan in 2014 to treat PHPT cases. However, there have been few reports on the outcomes. In our present study, we investigated the efficacy and safety of cinacalcet in 61 PHPT patients who were treated with this agent at our hospital between January 2014 and March 2017. The corrected serum Ca and intact PTH levels were significantly reduced by this treatment, whereas the serum phosphorus levels significantly increased. There were no significant differences in the eGFR or urinary Ca to urinary creatinine ratio between baseline and the maintenance phase. In terms of bone mineral density, there were significant increases observed in the 16 cases for whom a baseline value was available, 11 of whom had been treated for osteoporosis. The most common adverse events from cinacalcet treatment were gastrointestinal symptom, such as nausea and appetite loss. Other adverse events included severe dehydration due to hypercalcemia, myalgia, hypocalcemia, and increased urinary calcium excretion. Seven patients were switched to surgical treatment, and the drug was discontinued in 9 other patients, due to adverse effects. Our present study findings demonstrate that cinacalcet is an effective therapeutic option for PHPT from the perspective of hypercalcemia improvement but that adverse gastrointestinal effects of this drug occur at a frequency of about 10%.

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Section: Discussionmentioning

confidence: 98%

Effectiveness and safety of cinacalcet for primary hyperparathyroidism: a single center experience

et al. 2019

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“…Administration of denosumab induces a transient increase in PTH values secondary to the serum calcium decrease in post-menopausal osteoporotic women with neither renal dysfunction nor primary hyperparathyroidism [18]. Prolongation of denosumab treatment in patients with primary hyperparathyroidism, which implies repeated transient increases in PTH levels, does not seem to have a stimulating effect on the PTH levels [19]. Very recently, a randomized double-blind trial compared denosumab, denosumab plus cinacalcet, or placebo, given for 1 year, in 45 patients with primary hyperparathyroidism [20].…”

Section: Discussionmentioning

confidence: 99%

Hypercalcemia upon denosumab withdrawal in primary hyperparathyroidism: a case report and literature review

et al. 2020

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Denosumab discontinuation is associated with a rapid increase in bone resorption and a decrease in bone mineral density. Spontaneous vertebral fractures may occur as a side effect of the rebound of bone resorption. Cases of rebound-linked hypercalcemia have also been described, moderate in women with osteoporosis and breast cancer and severe in children receiving oncological doses of denosumab. We report the case of an adult woman with primary hyperparathyroidism and moderate hypercalcemia, treated with denosumab for osteoporosis, who developed severe hypercalcemia and spontaneous vertebral fractures (SVFs) after denosumab discontinuation. An 86-year-old woman with densitometric osteoporosis was treated for 3 years with 60 mg of subcutaneous denosumab every 6 months. She was known to have primary hyperparathyroidism, with a serum albumin-corrected calcium of 2.82 mmol/l (NV 2.15-2.5) at the end of denosumab effect. Nine months after the last denosumab injection, she was hospitalized due to worsening overall health. Clinical evaluation revealed severe hypercalcemia (calcium 3.35 mmol/l). Very high values of bone turnover markers (BTMs) suggested a rebound effect due to denosumab discontinuation. An X-ray showed multiple new SVFs. After injection of denosumab 60 mg, serum calcium rapidly decreased and BTMs were dramatically reduced. A surgical approach by minimally invasive parathyroidectomy allowed for definite resolution of hyperparathyroidism and hypercalcemia. This case suggests that hypercalcemia can be a side consequence of denosumab discontinuation, which can become severe when other causes of hypercalcemia, such as primary hyperparathyroidism, are present.

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“…Definitively, early diagnosis of BT is definitively crucial to avoid unnecessary medical/surgical treatment. Denosumab therapy has been approved, with different administration regimens and doses, for the treatment of unresectable CGTB, as well as for osteoporosis in pHPT ( 10 ). Denosumab 120 mg injection once every 4 weeks is indicated as prevention of skeletal-related events in adults with advanced bone malignancies ( 3 ).…”

Section: Discussionmentioning

confidence: 99%

When primary hyperparathyroidism comes as good news

Gallo

Rosetti

Marcon³

et al. 2020

Endocrinology, Diabetes &Amp; Metabolism Case Reports

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Summary Brown tumors are osteoclastic, benign lesions characterized by fibrotic stroma, intense vascularization and multinucleated giant cells. They are the terminal expression of the bone remodelling process occurring in advanced hyperparathyroidism. Nowadays, due to earlier diagnosis, primary hyperparathyroidism keeps few of the classical manifestations and brown tumors are definitely unexpected. Thus, it may happen that they are misdiagnosed as primary or metastatic bone cancer. Besides bone imaging, endocrine evaluation including measurement of serum parathyroid hormone and calcium (Ca) levels supports the pathologist to address the diagnosis. Herein, a case of multiple large brown tumors misdiagnosed as a non-treatable osteosarcoma is described, with special regards to diagnostic work-up. After selective parathyroidectomy, treatment with denosumab was initiated and a regular follow-up was established. The central role of multidisciplinary approach involving pathologist, endocrinologist and oncologist in the diagnostic and therapeutic work-up is reported. In our opinion, the discussion of this case would be functional especially for clinicians and pathologists not used to the differential diagnosis in uncommon bone disorders. Learning points: Brown tumors develop during the remodelling process of bone in advanced and long-lasting primary or secondary hyperparathyroidism. Although rare, they should be considered during the challenging diagnostic work-up of giant cell lesions. Coexistence of high parathyroid hormone levels and hypercalcemia in primary hyperparathyroidism is crucial for the diagnosis. A detailed imaging study includes bone X-ray, bone scintiscan and total body CT; to rule out bone malignancy, evaluation of bone lesion biopsy should include immunostaining for neoplastic markers as H3G34W and Ki67 index. If primary hyperparathyroidism is confirmed, selective parathyroidectomy is the first-line treatment. In advanced bone disease, treatment with denosumab should be considered, ensuring a strict control of Ca levels.

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Protective Effect of Denosumab on Bone in Older Women with Primary Hyperparathyroidism

Abstract: Denosumab therapy is effective in older women with PHPT-related osteoporosis.

Cited by 55 publications

References 35 publications

Effectiveness and safety of cinacalcet for primary hyperparathyroidism: a single center experience

Effectiveness and safety of cinacalcet for primary hyperparathyroidism: a single center experience

Hypercalcemia upon denosumab withdrawal in primary hyperparathyroidism: a case report and literature review

When primary hyperparathyroidism comes as good news

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