Table 5.

Experts’ advices on treatment modalities by setting

Non-metastatic disease	Metastatic disease
Therapeutic thresholds and modalities are the same for M0 HSPC and M0 CRPC	In the setting of M1 HSPC, the therapeutic schedule of BTTs is that used for osteoporosis (the same of M0 CRPC), not for metastases
Before starting any therapy specifically targeting the bone, evaluate and normalise the levels of vitamin D (≥30 ng/mL) during hormonal therapy, regardless of the bone-modifying agent	Intervention for metastatic disease in M1 CRPC is indicated at the time of diagnosis of the first metastasis as per all guidelines, and it is aimed at reducing SREs; the regimen employed both for ZA and DNB will widely cover also the possibility to reduce the risk of fragility fractures (benign fractures)
Vitamin D supplementation during bone-modifying agents is mandatory	In case of M1 CRPC, consider the opportunity to continue therapy with bone-modifying agents adjusting the dosages for bone health in case of discontinuation of SRE-specific treatment. In particular, caution must be paid when using DNB
Do not consider vitamin D and calcium supplementation as sufficient to maintain bone health or prevent fragility fractures
Physical activity and an adequate calcium intake are advised to avoid weight gain, reduce the risk of fall and for the likely positive impact on bone health
The posology used for DNB is the same used in case of osteoporosis in both men and women; for a BP, a wide spectrum of doses has been proposed, sometimes even higher than those used for osteoporosis
Start treatment with bone-modifying agents as soon as possible regardless of BMD even in M0 HSPC (no strict recommendations exist on PCa)

Unless specified, advices are valid for both settings. For detailed explanation, see the text.

BMD, bone mineral density; BP, bisphosphonate; BTT, bone turnover inhibitor; CRPC, castration-resistant prostate cancer; DNB, denosumab; HSPC, hormone-sensitive prostate cancer; M0, non-metastatic; M1, metastatic; PCa, prostate cancer; SRE, skeletal-related event; ZA, zoledronic acid.