Lab-made hormone may help some children with hypoparathyroidism
Teriparatide use suggested for youngsters not responding to supplements
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The use of teriparatide, a lab-made version of the parathyroid hormone — low levels of which lead to hypoparathyroidism — should not replace supplement therapy in children with the rare condition, but may benefit young patients who don’t respond well to standard care.
That’s the key takeaway from a new review of published studies by two researchers, who found that teriparatide maintained blood calcium levels similarly to standard supplement treatment while also lowering phosphate levels. The duo noted, however, that while the analysis found growth and bone density overall remained within the normal range with the lab-made hormone, kidney outcomes were inconsistent across studies.
Thus, despite the generally promising results, the scientists — one in the U.S. and the other in Thailand — stopped short of recommending teriparatide as a routine replacement for standard treatment. Instead, they suggested reserving the hormone’s use for children who experience persistent symptoms or side effects with supplements.
“In children with chronic hypoparathyroidism, teriparatide … may be particularly beneficial in patients with suboptimal [symptom] control … on conventional therapy,” the team wrote.
The researchers said their review was hampered by the “substantial [differences seen] in study design, and reported outcomes, which limited formal analysis of several clinically relevant endpoints,” or goals. Still, they noted that “given the rarity of pediatric chronic hypoparathyroidism, inclusion of diverse [studies] was necessary to capture the available evidence.”
Their study, titled “Teriparatide Therapy in Children with Hypoparathyroidism: A Systematic Review and Meta-Analysis,” was published in the journal Calcified Tissue International.
In people with hypoparathyroidism, the parathyroid glands — four pea-sized organs located in the neck — don’t produce enough parathyroid hormone, or PTH. This leads to low calcium, called hypocalcemia, and high phosphate, known as hyperphosphatemia, in the bloodstream, and causes a wide range of symptoms.
Synthetic teriparatide replaces missing PTH hormone
Prescribing supplements of calcium and active vitamin D has long been the standard treatment for hypoparathyroidism. This approach, however, does not replace the missing hormone. Additionally, excess calcium can spill over into the urine, a condition known as hypercalciuria, which increases the risk of kidney stones.
Teriparatide, a synthetic form of PTH known as PTH 1-34 — commonly sold under brand names such as Forteo or Bonsity — is designed to replace the missing hormone. Given subcutaneously, or as an under-the-skin injection, it’s widely approved for treating osteoporosis, a condition marked by brittle bones that easily fracture.
More recently, a version of PTH 1-34 called Yorvipath (palopegteriparatide), modified to last longer in the bloodstream, has been approved for adults with hypoparathyroidism. Still, neither teriparatide nor Yorvipath is cleared for use in children with the condition.
In one small study involving 10 youngsters with hypoparathyroidism who failed to respond to standard supplement treatment, off-label use of teriparatide significantly improved calcium and phosphate control, data showed.
Now, to further assess the effectiveness of teriparatide in this pediatric patient population, the researchers — one from Boston Children’s Hospital and Harvard Medical School and the other from Mahidol University in Bangkok — gathered data from 18 published studies. The duo examined the outcomes of 94 children diagnosed with hypoparathyroidism who received teriparatide treatment for at least four weeks.
The most common hypoparathyroidism causes among the youngsters were autoimmune polyglandular syndrome type 1 (APS-1) and a mutation in the calcium-sensing receptor gene known as CASR. Each accounted for 34% of the cases.
Blood calcium levels comparable with hormone vs. standard treatment
When the researchers pooled data from six studies, they found no significant difference in blood calcium levels between children on teriparatide and those on standard therapy. Blood phosphate levels, in contrast, were lower with teriparatide treatment.
While results on urinary calcium were mixed in the pooled analysis, longer-term studies following patients for more than two years suggested reductions over time, the researchers noted.
Growth and bone mineral density generally stayed within normal ranges across the studies. A bone formation marker called alkaline phosphatase was higher in children on teriparatide than in those on standard therapy. Still, height scores showed no significant difference between groups.
Kidney outcomes varied across studies, the researchers noted. Some showed stable findings with no new calcium deposits in the kidneys, while others reported new or worsening deposits in a subset of patients. For example, one study found progression of kidney calcium deposits in two of six patients after nine years of follow-up, and another found progression in five of 12 patients over a mean follow-up of 6.9 years.
Some children received teriparatide via continuous subcutaneous pump rather than twice-daily injections. This pump-based approach, evaluated in five studies, appeared to achieve calcium control and was associated with lower bone turnover markers compared with injections, per the data.
Requirements for active vitamin D and calcium supplements varied widely with teriparatide use, the data showed. Some patients stopped these treatments entirely, others had dose reductions, and some required active vitamin D reintroduction. With continuous pump delivery, active vitamin D and calcium were generally discontinued.
Current evidence suggests that teriparatide may be a promising alternative for selected children with chronic hypoparathyroidism.
The authors noted that teriparatide initially carried a black box warning for a type of bone cancer known as osteosarcoma based on rat studies using very high doses. Still, this warning was later removed for adults after surveillance studies found no increased risk. The review found no reported cases of osteosarcoma among children treated with teriparatide, including when follow-up lasted 13.5 years.
Overall, “current evidence suggests that teriparatide may be a promising alternative for selected children with chronic hypoparathyroidism,” the researchers concluded. However, given the lack of comparative studies, the duo recommended that “conventional therapy should remain the standard of care.”
The team urged that the synthetic hormone “be considered in … patients with persistent symptoms, treatment-related complications, or challenges with adherence to conventional therapy.”
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