Long-Term Treatment of Hypoparathyroidism: A Randomized Controlled Study Comparing Parathyroid Hormone-(1–34)<i>Versus</i>Calcitriol and Calcium

Winer, Karen K.; Ko, Chia‐Wen; Reynolds, James C.; Dowdy, Karen; Keil, Meg; Peterson, Donna; Gerber, Lynn H.; McGarvey, Charles L.; Cutler, Gordon B.

doi:10.1210/jc.2002-021736

Cited by 291 publications

(265 citation statements)

References 23 publications

Supporting

Mentioning

236

Contrasting

Unclassified

Order By: Relevance

“…(36) Several small teriparatide studies ranging from 20 weeks to 3 years have shown better control of serum calcium levels along with reduced needs for calcium and vitamin D supplementation when compared to calcium and vitamin D supplementation alone. (37)(38)(39)(40) PTH(1-84) has also shown promising results for the treatment of hypoparathyroidism. Several recent clinical trials have shown a reduced need for vitamin D and/or calcium supplementation as well as improvement in abnormal bone remodeling and metabolism on daily or every other day dosing.…”

Section: Use In Hypoparathyroidismmentioning

confidence: 99%

“…(38)(39)(40)(41)(42)47,85) Winer and colleagues (39) reported no cases of high serum or urinary calcium levels in hypoparathyroid patients treated with teriparatide twice daily over a 3-year period. Data from PTH(1-84) trials showed transient episodes of mild hypercalcemia, accounting for only 4% of all measurements and a significant but minimal and isolated 3-month increase in urinary calcium excretion among 30 subjects receiving the hormone at the dose of 100 mg every other day for 24 months.…”

Section: Safety In Hypoparathyroidism Trialsmentioning

confidence: 99%

See 1 more Smart Citation

Safety of osteoanabolic therapy: A decade of experience

Capriani

Irani

Bilezikian

2012

Journal of Bone and Mineral Research

132

View full text Add to dashboard Cite

IntroductionO steoporosis is a prevalent disease that affects more than 10 million Americans. The lifetime risk of an osteoporosisrelated fracture is 50% for Caucasian women and 25% for men. Hip fractures carry a 10% to 20% increase in mortality rate within the first year after fracture. (1) The burden of the hip and other fractures can result in chronic pain, disability and other indices of reduced quality of life.Amidst these sobering statistics is the welcome advent over the past two decades of effective pharmacological therapies that reduce fracture risk. The therapies approved for the management of osteoporosis include bisphosphonates, raloxifene (a selective estrogen-receptor modulator), calcitonin, denosumab, strontium ranelate, and parathyroid hormone and PTH(1-84)]. The fulllength PTH molecule and its foreshortened amino-terminal fragment (teriparatide) are currently the only osteoanabolic agents approved for use. PTH(1-84) is not available in the United States. In November, 2002, teriparatide was approved by the U.S. Food and Drug Administration (FDA) for the treatment of postmenopausal osteoporosis and, later, in men. The approval came with restrictions in duration of therapy (18-24 months) and was limited to individuals with advanced osteoporosis at high risk for fracture. Reasons for these limitations relate, at least in part, to the unexpected occurrence of osteosarcoma and other bone neoplasms in Fischer 344 rat toxicity studies. In fact, the pivotal phase 3 trial of teriparatide was suspended when these rat toxicity data became available. The effects on rats was doseand duration-dependent, with rats being treated for approximately 80% of their lifetime and at doses three to 58 times the currently approved human dose. (2) Similar toxicity was seen for PTH(1-84) (3) Given the clear-cut efficacy data when the results of the abbreviated clinical trial results for teriparatide were analyzed, the FDA and equivalent other agencies in Europe and elsewhere granted approval of teriparatide with the stipulations that it should be used for no longer than 2 years. In the United States, the drug carries a ''black box warning'' and contraindicates its use in patients with existing risk factors for osteosarcoma, including Paget's disease of bone, prior skeletal radiation, and children with open epiphyses.Teriparatide has now been used in the United States for 10 years. With a decade of experience, it is timely to review the efficacy and safety profile of this medication. PTH(1-84) will also be reviewed. This perspective will be limited to PTH formulations that are available for the treatment of osteoporosis; we will not be discussing other anabolic agents that are currently being studied but are not yet approved, such as the sclerostin antibody (http://clinicaltrials.gov/ct2/results?term ¼ sclerostin þ anti-þ antibody). PTH mechanisms of actionTeriparatide is an amino-terminal fragment of PTH that is biologically identical to the amino-terminal fragment of human PTH. This fragment contains all the classical bio...

show abstract

Section: Use In Hypoparathyroidismmentioning

confidence: 99%

Section: Safety In Hypoparathyroidism Trialsmentioning

confidence: 99%

Safety of osteoanabolic therapy: A decade of experience

Capriani

Irani

Bilezikian

2012

Journal of Bone and Mineral Research

132

View full text Add to dashboard Cite

show abstract

“…It has been reported that 5 to 53% of rats treated with high dose PTH for 2 years developed osteosarcoma [25,26]. On the contrary, Winer et al reported that three-year treatment in patients with hypoparathyroidism with twice daily subcutaneous PTH provided long-term normalization of the serum calcium and urinary calcium levels without apparent adverse effects on the bone [27]. For safety sake, indications of PTH administration for the patients with gain-of-function mutations of the CaR should be limited to those who have severe hypocalcemia with tetanic symptoms in spite of 1,25(OH) 2 D 3 administration.…”

Section: Discussionmentioning

confidence: 99%

Effect of Parathyroid Hormone Administration in a Patient with Severe Hypoparathyroidism Caused by Gain-of-function Mutation of Calcium-sensing Receptor

et al. 2006

View full text Add to dashboard Cite

Abstract. Hypoparathyroidism caused by gain-of-function mutations of the calcium-sensing receptor (CaR) in the transmembrane domain is usually severe and difficult to manage. A patient with severe hypoparathyroidism, caused by CaR activating mutation F821L, was treated for 3 days (Day 1 to Day 3) with synthetic human parathyroid hormone 1-34 (teriparatide, PTH). An Ellsworth-Howard test of the patient revealed normal responses of urine phosphate and cyclic AMP excretion, indicating that the patient's renal tubules normally responded to extrinsic PTH. On Day 1 to Day 3, 0.9 µg/kg/day of PTH was administered subcutaneously twice daily at 0800 and 2000. On Day 1, the serum calcium level that was 1.8 mmol/l before PTH administration increased to 2.1 mmol/l at 1200, and gradually decreased to 1.8 mmol/l at 2000. On Days 2 and 3, the maximum calcium levels were 2.5 and 2.4 mmol/l, respectively, at 1200. At 2000, they returned to or below basal levels at 0800. On Day 4 without PTH administration, the calcium levels were maintained at the basal levels at Day 0. The urine calcium/creatinine (Ca/Cr) ratio that was high (>0.4) before PTH injection decreased after PTH administration (0.4>). Changes in the ionized calcium levels were almost parallel with the total calcium levels. The serum inorganic phosphate (IP) level decreased to 2.4 mmol/l at 1000, but gradually increased before the second PTH injection to the level at 0800 on Day 1. The minimum IP level on Days 2 and 3 was 2.1 mmol/l and 2.0 mmol/l, respectively. In contrast to the remarkable changes in the serum calcium level by PTH treatment, the serum magnesium levels showed few changes. These results indicate that PTH therapy could be effective in correcting serum and urine calcium and the phosphate levels in hypoparathyroidism caused by activating mutation of CaR.

show abstract

“…PTH treatment has the advantage of normalizing calcemia without increasing calciuria, reducing the risk of nephrocalcinosis and renal insufficiency, and, theoretically, the antagonists of the calcium sensor receptor may be utilized in the treatment to promote the inactivation of the receptor and, consequently, increase PTH secretion, but there still have not been sufficient studies (40). …”

Section: Treatment Of Hypocalcemiamentioning

confidence: 99%

Hypoparathyroidism and pseudohypoparathyroidism

Maeda

Fortes

Oliveira

et al. 2006

Arq Bras Endocrinol Metab

View full text Add to dashboard Cite

The principal function of the parathyroid hormone (PTH) is maintenance of calcium plasmatic levels, withdrawing the calcium from bone tissue, reabsorbing it from the glomerular filtrate, and indirectly increasing its intestinal absorption by stimulating active vitamin D (calcitriol) production. Additionally, the PTH prompts an increase in urinary excretion of phosphorus and bicarbonate, seeking a larger quantity of free calcium available in circulation. Two mechanisms may alter its function, limiting its control on calcium: insufficient PTH production by the parathyroids (hypoparathyroidism), or a resistance against its action in target tissues (pseudohypoparathyroidism). In both cases, there are significantly reduced levels of plasmatic calcium associated with hyperphosphatemia. Clinical cases are characterized by nervous hyperexcitability, with paresthesia, cramps, tetany, hyperreflexia, convulsions, and tetanic crisis. Abnormalities such as cataracts and basal ganglia calcification are also typical of these diseases. Treatment consists of oral calcium supplementation associated with increased doses of vitamin D derivatives. A principal função do paratormônio (PTH) é a manutenção dos níveis plasmáticos de cálcio, retirando-o do tecido ósseo, reabsorvendo-o do filtrado glomerular e, indiretamente, aumentando sua absorção intestinal através do estímulo para a produção de vitamina D ativa (calcitriol). Além disso, o PTH promove um aumento na excreção urinária de fósforo e bicarbonato, objetivando uma maior quantidade de cálcio livre disponível na circulação. Dois mecanismos podem alterar sua função, limitando seu controle sobre o cálcio: produção insuficiente de PTH pelas paratiróides (hipoparatiroidismo), ou uma resistência à sua ação nos órgãos-alvo (pseudohipoparatiroidismo). Em ambos os casos, ocorre uma redução significativa dos níveis plasmáticos de cálcio em associação com hiperfosfatemia. Manifestações clínicas características são: hiperexcitabilidade nervosa, com parestesia, cãimbras, tetania, hiperreflexia, convulsões e crise tetânica. Catarata e calcificação dos gânglios basais são anormalidades típicas dessas doenças. O tratamento consiste da suplementação oral de cálcio, associada com doses elevadas de derivados da vitamina D.

show abstract

Long-Term Treatment of Hypoparathyroidism: A Randomized Controlled Study Comparing Parathyroid Hormone-(1–34)VersusCalcitriol and Calcium

Cited by 291 publications

References 23 publications

Safety of osteoanabolic therapy: A decade of experience

Safety of osteoanabolic therapy: A decade of experience

Effect of Parathyroid Hormone Administration in a Patient with Severe Hypoparathyroidism Caused by Gain-of-function Mutation of Calcium-sensing Receptor

Hypoparathyroidism and pseudohypoparathyroidism

Contact Info

Product

Resources

About