Prolia (Denosumab) Appetite & Cravings Changes: What the Evidence Actually Shows

Does Prolia cause appetite changes or cravings?

Appetite change and cravings are not established effects of Prolia [1][2]. In the Prolia label, the table of adverse reactions occurring in at least 2% of postmenopausal women and more often than placebo lists back pain (34.7% vs 34.6%), pain in extremity (11.7% vs 11.1%), musculoskeletal pain (7.6% vs 7.5%), hypercholesterolemia (7.2% vs 6.1%), and cystitis (5.9% vs 5.8%) [1]. The gastrointestinal terms in that table are upper abdominal pain (3.3% vs 2.9%), flatulence (2.2% vs 1.4%), and GERD (2.1% vs 1.7%); appetite change and cravings are not listed [1].

FREEDOM randomized 7,868 postmenopausal women to denosumab 60 mg or placebo every 6 months for 36 months, with new vertebral fracture as the primary endpoint [2]. The abstract's reported results are fracture outcomes, not appetite or craving measures [2].

Why does the Xgeva label mention nausea or decreased appetite?

Those terms come from the Xgeva label, a different product. Xgeva is 120 mg subcutaneously every 4 weeks for cancer-related bone conditions, giant cell tumor of bone, and hypercalcemia of malignancy; it is not an osteoporosis drug [3]. In pooled Xgeva trials involving patients with bone metastases from solid tumors or lytic bone lesions from multiple myeloma, nausea was reported in 31% of Xgeva recipients versus 32% of zoledronic acid recipients [3]. The Xgeva label also lists decreased appetite among the most common reactions in hypercalcemia of malignancy [3]. Those figures do not apply to Prolia 60 mg every 6 months.

Could another medicine explain appetite changes?

Glucocorticoid-induced osteoporosis is one of Prolia's indications [1]. Glucocorticoids can increase food intake: in a randomized study of 20 healthy men, 4 days of oral methylprednisolone 40 mg daily increased ad libitum energy intake compared with placebo (4,554 vs 2,867 kcal/day; P=0.04) [5]. That study did not involve Prolia, so it does not show what happens in people taking both medicines.

What about hypocalcemia and stopping Prolia?

Prolia carries a boxed warning for severe hypocalcemia in patients with advanced chronic kidney disease (eGFR below 30), including dialysis-dependent patients [1]. The FDA lists hypocalcemia symptoms as confusion, seizures, irregular heart rhythm, fainting, face twitching, uncontrolled muscle spasms, weakness, tingling, or numbness; appetite change and cravings are not on that list [4]. The label says pre-existing hypocalcemia must be corrected before starting, and that all patients should take calcium 1,000 mg daily and at least 400 IU vitamin D daily [1].

The label also says that if Prolia is discontinued, patients should transition to an alternative antiresorptive therapy; new vertebral fractures have occurred as early as 7 months after the last dose, and multiple vertebral fractures can occur after discontinuation [1]. This warning is about fracture risk, not appetite.