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Hyperparathyroidism Due to the So-Called Bone Hunger Syndrome in Prostate Cancer Patients

Dipartimento di Scienze Cliniche e Biologiche, Università di, Torino, Oncologia Medica, Medicina Interna, Urologia, Azienda, Ospedaliera San Luigi 10043 Orbassano, Italy

Address correspondence to: Luigi Dogliotti, M.D., Dipartimento di Scienze Cliniche e Biologiche, Università di Torino, Oncologia Medica, Azienda Ospedaliera San Luigi, Regione Gonzole 10, 10043 Orbassano, Italy. E-mail: .

To the editor:

The bone hunger syndrome is a well recognized metabolic derangement that may complicate the natural history of prostate cancer patients with bone metastases. It is characterized by calcium entrapment in bone as a consequence of excessive osteoblastic activity that leads to hyperparathyroidism in response to calcium demand. PTH elevation stimulates osteoclasts at sites distant to those involved by the tumor. The incidence of this metabolic derangement in bone metastatic prostate cancer patients is unknown. In their recent article in JCEM, Murray et al. (1) measured serum PTH, calcium ionized and urinary deoxypyridinolines (DPYDs) in 131 advanced prostate cancer patients. They showed that 34% of these patients had elevated PTH values. Patients with proven bone metastases had significantly higher PTH levels than those without, and there was a trend of higher PTH levels in favor of patients with progressive disease as opposed to those with disease response or disease stabilization. Mean levels of urinary DPYD were significantly greater in patients with high PTH than those with a normal PTH. Treatment with oral calcium supplements in patients with elevated PTH was scarcely effective in lowering circulating PTH and raising calcium values. The authors concluded that secondary hyperparathyroidism occurs frequently in patients with prostate cancer and is inadequately controlled by calcium supplementation. They also speculated that this metabolic disturbance may limit the efficacy of bisphosphonates because these drugs per se may lead to PTH elevation, thus worsening the pre-existing hyperparathyroidism. The study of Murray et al. (1) is interesting, but the last speculation is questionable. Notwithstanding the osteoblastic nature, increasing evidence indicates that bone resorption is also increased in prostate cancer patients with bone metastases, favoring the occurrence of skeletal complications. Bisphosphonates are therefore destined to become new effective drugs in the management of metabolic bone disease induced by prostate cancer (2). A few years ago we performed a metabolic study in which a single dose of pamidronate was administered to a number of prostatic cancer patients with bone metastases. Bone resorption and formation markers were monitored in the following weeks (3). As expected, we observed a prompt and significant reduction in urinary markers of bone collagen breakdown [DPYDs and N-telopeptide of type I collagen (NTX)], but a somewhat unexpected finding was the reduction in bone alkaline phosphatase that followed by some weeks the DPYD and NTX reduction. The reduction in bone formation after bisphosphonate administration has been discussed by Vinholes et al (4); these authors suggested that the bisphosphonate-mediated decrease in bone formation could be due to the blockade of the resorptive arm of remodeling cycle, because the direct effect upon osteoblastic function is little, if any. Whatever is the mechanism, the decrease in bone formation may reduce the calcium demand in bone, thus improving the secondary hyperparathyroidism due to the bone hunger syndrome. On these grounds, we treated with pamidronate a patient bearing prostate cancer with blastic bone metastases and a biochemical picture of bone hunger syndrome, i.e. elevation of serum bone alkaline phosphatase, serum PTH, and urinary bone resorption markers DPYD and NTX, associated with low levels of serum calcium, serum phosphorus, and urinary calcium/creatinine (5). After pamidronate infusion (60 mg iv every 3 wk, for a total of four times), bone alkaline phosphatase and PTH decreased consistently, serum calcium and phosphorous returned within normality, whereas markers of bone collagen breakdown showed a significant decrease preceded by a transient rise. These data suggest that bisphosphonates, by reducing the bone metabolic derangement, may be effective in the treatment of hypocalcemia tendency and hyperparathyroidism that accompany prostate cancer patients. A prospective clinical trial in this patient subgroup is therefore mandatory.

Received December 14, 2001.

References

1. Murray RML, Grill V, Crinis N, Ho PW, Davison J, Pitt P 2001 Hypocalcemic and normocalcemic hyperparathyroidism in patients with advanced prostate cancer. J Clin Endocrinol Metab 86:4133–4138[Abstract/Free Full Text]
2. Berruti A, Dogliotti L, Tucci M, Tarabuzzi R, Fontana D, Angeli A 2001 Metabolic bone disease induced by prostate cancer. Rationale for the use of bisphosphonates. J Urol 166:2023–2031[CrossRef][Medline]
3. Berruti A, Sperone P, Cerutti S, Torta M, Gorzegno G, Bottini A, Dogliotti L, Angeli A, Pamidronate administration to bone metastatic prostate cancer patients improves bone metabolic derangement and bone pain. Proceedings of the 33rd Annual Meeting of the American Society for Clinical Oncology, 1997, Denver, CO, p 59a (Abstract 206)
4. Vinholes J, Coleman R, Eastell R 1996 Effects of bone metastases on bone metabolism: implications for diagnosis, imaging and assessment of response to cancer treatment. Cancer Treat Rev 22:289–331[CrossRef][Medline]
5. Berruti A, Sperone P, Fasolis G, Torta M, Fontana D, Dogliotti L, Angeli A 1997 Pamidronate administration improves the secondary hyperparathyroidism due to "bone hunger syndrome" in a patient with osteoblastic metastases from prostate cancer. Prostate 33:252–255[Medline]

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