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Focus on Primary Hyperparathyroidism – Diagnosis, Management and the Role of Calcimimetics
blind study in 78 patients with mild to moderate primary HPT,
15
These data indicate that cinacalcet may be of benefit in a wide range
normocalcaemia (serum calcium ≤2.57 mmol/l [10.3mg/dl]) plus a of patients with primary HPT, offering a novel alternative option for
reduction of at least 0.12mmol/l (0.5mg/dl) from baseline was those who are not able to undergo parathyroidectomy despite
achieved by 73% of patients in the cinacalcet group compared with meeting the clinical criteria.
only 5% of placebo recipients (p<0.001). This effect was sustained,
with constant serum calcium maintained once steady state was Conclusions
reached. Mean pre-dose serum PTH levels were reduced by Optimal management of primary HPT is an evolving challenge for
approximately 8% in the cinacalcet group but not into the normal physicians, with the changing presentation of this disease leading to
range and increased by 8% in the placebo arm. Markers of bone questions regarding the most appropriate choice of treatment. The
turnover increased slightly in the cinacalcet group, but BMD advent of new management guidelines for individuals with asymptomatic
remained unchanged overall between the treatment arms. primary HPT, as well as novel pharmacological options such as
Cinacalcet was generally well tolerated with a similar adverse event cinacalcet, heralds a positive new era for this patient group. n
profile to the placebo group.
Peter Schwarz is Professor and Consultant at the
A four-year open-label extension study found that cinacalcet was
Osteoporosis Outpatient Clinic and Director of the
well tolerated and provided long-term control of serum calcium Research Centre of Ageing and Osteoporosis,
levels. Eighty per cent of patients had serum calcium levels within
Department of Geriatrics and Rheumatology at Glostrup
Hospital. His research interests include calcium
the normal range at study end (see Figure 2), while serum PTH was
homeostasis and bone disease. He is President of the
reduced slightly (9%).
16
Although BMD did not increase, there was Science Faculty of the Danish Society of Geriatrics, a
no excess bone loss and no evidence that parathyroid gland mass
Section Editor (Medicine) for the Scandinavian Journal of
Medicine and Science in Sports and a member of the
increased. Of particular interest, the dose of cinacalcet remained
scientific board of the Scandinavian Journal of Clinical and
stable at 30mg twice daily. Laboratory Investigation.
Roger Bouillon is Professor and Chairman of
In patients with intractable primary HPT (Ca >3.1mmol/l [12.5mg/dl]
Endocrinology (internal medicine) at the University and
with no other treatment options),
17
cinacalcet (30mg twice daily, the University Hospital of the Catholic University of
titrated to a maximum of 90mg four times a day) induced marked
Leuven. His research covers various aspects of bone and
calcium homeostasis, and his primary interest is
decreases in serum calcium, with 15 of 17 patients achieving
hormonal regulation of bone metabolism and vitamin D.
reductions of ≥0.25mmol/l (≥1mg/dl). Importantly, health- He is a member of the Royal Academy of Medicine
related quality of life (HRQoL) also improved.
17
These results
(Belgium), a Fellow of the Royal College of Physicians,
London, Vice President of the International Bone and
led to cinacalcet being approved by European regulatory
Mineral Society and a board member of the Vitamin D
authorities in 2008 for the treatment of patients with primary Workshop Inc.
HPT for whom parathyroidectomy would be indicated on the basis
of serum calcium levels (as defined by relevant treatment
Munro Peacock is Professor of Medicine and Director of
the General Clinical Research Center at Indiana University.
guidelines), but in whom parathyroidectomy is not clinically
His current research interests include genetics of bone
appropriate or is contraindicated.
19
mass, mineral homeostasis, mineral accreditation in
adolescents and clinical use of calcimimetics. A Fellow of
the Royal College of Physicians, London, Professor
In addition, cinacalcet has been shown to be effective in patients with
Peacock has to date published 347 papers in the fields of
inoperable parathyroid carcinoma (n=29).
18
Sixty-two per cent of mineral metabolism and mineral endocrinology. He
patients had reductions in serum calcium (≥1mg/dl) at the end of the
gained his medical degree from the University of Glasgow
and holds a DSc from the University of Glasgow and from
titration period, with the greatest reductions noted in those patients
Purdue University in Indiana.
with the highest baseline calcium.
18
1. Perrier ND, Asymptomatic hyperparathyroidism: a Third International Workshop, J Clin Endocrinol Metab, 14. Wuthrich RP, Martin D, Bilezikian JP, The role of
medical misnomer?, Surgery, 2005;137:127–31. 2009;94:335–9. calcimimetics in the treatment of hyperparathyroidism,
2. Sosa JA, Udelsman R, New directions in the treatment of 8. Eastell R, Arnold A, Brandi ML, et al., Diagnosis of Eur J Clin Invest, 2007;37:915–22.
patients with primary hyperparathyroidism, Curr Probl asymptomatic primary hyperparathyroidism: 15. Peacock M, Bilezikian JP, Klassen PS, et al., Cinacalcet
Surg, 2003;40:812–49. proceedings of the Third International Workshop, J Clin hydrochloride maintains long-term normocalcaemia in
3. Farford B, Presutti RJ, Moraghan TJ, Nonsurgical Endocrinol Metab, 2009;94:340–50. patients with primary hyperparathyroidism, J Clin
Management of Primary Hyperparathyroidism, Mayo Clin 9. Udelsman R, Pasieka JL, Sturgeon C, et al., Surgery for Endocrinol Metab, 2005;90:135–41.
Proc, 2007;82:351–5. asymptomatic primary hyperparathyroidism: 16. Peacock M, Scumpia S, Bolognese MA, et al., Long-term
4. Silverberg SJ, Lewiecki M, Mosekilde L, et al., proceedings of the Third International Workshop, J Clin control of primary hyperparathyroidism with cinacalcet,
Presentation of asymptomatic primary Endocrinol Metab, 2009;94:366–72. American Society for Bone and Mineral Research, 2006:
hyperparathyroidism: proceedings of the Third 10. Khan AA, Grey A, Shoback D, Medical management of abstract 1137.
International Workshop, J Clin Endocrinol Metab, primary hyperparathyroidism: proceedings of the Third 17. Marcocci C, Chanson P, Shoback D, et al., Cinacalcet
2009;94:351–65. International Workshop, J Clin Endocrinol Metab, 2009;94: reduces serum calcium concentrations in patients with
5. Adami S, Marcocci C, Gatti D, Epidemiology of primary 373–81. intractable primary hyperparathyroidism, J Clin Endocrin
hyperparathyroidism in Europe, J Bone Miner Res, 11. Patel S, Current and potential future drug treatments Metab, 2009;doi;10.1210/jc.2008–2640.
2002;17(Suppl. 2):N18–23. for osteoporosis, Ann Rheum Dis, 1996;55:700–14. 18. Silverberg SJ, Rubin MR, Faiman C, et al., Cinacalcet
6. Khan AA, Bilezikian JP, Potts JT, The diagnosis and 12. Russell RG, Bisphosphonates: Mode of Action hydrochloride reduces the serum calcium concentration
management of asymptomatic primary and Pharmacology, Pediatrics, 2007;119(Suppl. 2): in inoperable parathyroid carcinoma, J Clin Endocrinol
hyperparathyroidism revisited, J Clin Endocrinol Metab, S150–S162. Metab, 2007;92:3803–8.
2009;94:333–4. 13. Nemeth EF, Steffey ME, Hammerland LG, et al., 19. EMEA: Mimpara (cinacalcet hydrochloride) Summary of
7. Bilezikian JP, Khan AA, Potts JT, Guidelines for the Calcimimetics with potent and selective activity on the Product Characteristics, 2009.
management of asymptomatic primary parathyroid calcium receptor, Proc Natl Acad Sci U S A,
hyperparathyroidism: summary statement from the 1998;95:4040–45.
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