PTH Replacement Therapy Leads to Better Life Quality: Meta-analysis
Treatment appears effective in controlling calcium and phosphate levels
Replacement therapy with either Forteo or Natpara, two versions of the parathyroid hormone (PTH), appears to be safe and effective in controlling calcium and phosphorus pools in the body, and this translates to better quality of life for patients with hypoparathyroidism, a meta-analysis study has found.
Hypoparathyroidism happens as a result of a deficiency of PTH, a hormone that helps the body control circulating levels of calcium, phosphorus, and vitamin D. Patients with hypoparathyroidism have low blood levels of calcium and high blood levels of phosphate, a molecule that contains phosphorus. They also have low vitamin D.
Often, the symptoms of hypoparathyroidism are treated with supplements of calcium and calcitriol (the active form of vitamin D). However, the supplements fail to control the levels of phosphate, and this may cause complications, mainly to the kidneys.
Replacing PTH with a lab-made version of the hormone is an alternative option, but the ideal therapy has yet to be found. Currently, PTH replacement is indicated as second-line therapy only for patients who do not respond well to calcium and calcitriol alone.
What was included in the meta-analysis?
Now, a team of researchers in Italy set out to determine how well two versions of PTH, called Forteo (teriparatide) — approved for the treatment of osteoporosis but also used in hypoparathyroidism — and Natpara work to restore the balance of calcium, phosphorus, and vitamin D in patients with hypoparathyroidism.
They used a method of analysis, called a meta-analysis, to combine data from a total of 588 patients, ages 7 to 78, who took part in 36 different studies published from January 1996 to March 2021. Twenty-six studies were funded by pharmaceutical companies.
There were 242 patients (about a quarter of them were male) from randomized controlled trials, and 343 patients (262 female and 81 male) from non-randomized controlled trials. A randomized controlled trial means one that uses a control group and assigns participants randomly to study groups.
The most common cause of hypoparathyroidism was surgery, followed by unknown (idiopathic), autoimmune, and genetic causes.
The dose of Forteo ranged from 20 to 40 micrograms (mcg) in adults and from 0.4 to 1.2 mcg per kilogram of body weight in children, most often given two times per day. The Natpara dose ranged from 25 to 100 mcg, given once per day or every other day.
First, the researchers looked at blood calcium levels. Data from nine studies (161 patients), seven on Forteo and two on Natpara, revealed that PTH replacement therapy had no significant effect on blood calcium levels.
However, when they looked at how much calcium was eliminated through the urine, they found that it was reduced in patients treated with PTH replacement therapy, meaning that more calcium was being retained by the body. Data came from 13 studies (313 patients), nine on Forteo and four on Natpara, and there were no differences between the two versions of PTH.
Next, the data from 12 studies (254 patients), nine on Forteo and three on Natpara, revealed that PTH replacement therapy significantly lowered blood phosphate levels, and that the two therapies were equally effective.
The researchers also looked at the calcium-phosphate product, a marker of cardiovascular risk in patients with kidney problems. Data from three studies (147 patients) on Natpara revealed that this version of PTH reduced the calcium-phosphate product.
PTH replacement therapy also increased bone turnover — the process of bone resorption followed by replacement with new bone. Three studies (65 patients) that looked at the amount of minerals in bone found that both Forteo and Natpara increased the amount of minerals in the lumbar spine.
Next, the researchers looked at data on calcium and calcitriol supplementation. Data from seven studies (177 patients), four on Forteo and three on Natpara, revealed that PTH replacement therapy allowed a reduction of the calcium dosage by a mean 1.63 grams per day. About half of the patients were able to discontinue calcium supplementation. Similar findings were obtained for calcitriol, although with a higher percentage of complete withdrawal of supplementation.
“These therapies also enabled the reduction or discontinuation of oral calcium and vitamin D supplementation,” the researchers wrote.
What were the effects of PTH replacement therapy?
When they looked at mental and physical quality of life, assessed using the 36-Item Short Form Health Survey (SF-36) in three studies (194 patients), the researchers found that it had significantly improved.
Serious side effects were reported in 11 studies (330 patients), with 30 patients reporting at least one serious side effect. Most were not considered to be related to PTH replacement therapy, and there was no increased risk of serious side effects in patients receiving PTH replacement therapy compared with controls.
“PTH replacement therapy is well-tolerated, safe and effective in the management of hypoparathyroidism,” the researchers concluded. “Unlike conventional supplementation, it has beneficial effects on serum [blood] phosphate, calcium–phosphate product and urinary calcium excretion, which are currently the unmet needs in chronic hypoparathyroidism.”
Despite limitations such as incomplete data and variability in the protocol design across studies, “our results support the use of PTH replacement therapy in patients in whom hyperphosphatemia [high blood phosphate] and increased urinary calcium excretion are a clinical concern,” they added.