Forteo 1-34 Teraparatide or 1-34 PTH
1-34 Teraparatide is recombinant human parathyroid hormone. 1-34 PTH stimulates bone growth directly. It causes rebuilding of the internal structure of bone caused by aggressive bone absorption not balanced by bone formation. This imbalance is mechanism of postmenopausal osteoporosis and is the cause of other forms of the disease too. 1-34 PTH is an effective therapy for osteoporosis in men and women. It treats the common Northern European genetic variety seen in white people as well as osteoporosis in an African American female with systemic lupus erythematosus or other autoimmune diseases. It has been shown to effectively treat osteoporosis caused by glucocorticoids. Teraparatide is a self-administered by daily injection. Patients usually find this daunting at first but quickly discover there is nothing to it. There are only a few minor side effects and no serious ones
Forteo Indications from the Product Label
Treatment of Postmenopausal Women with Osteoporosis at High Risk for Fracture
FORTEO is indicated for the treatment of postmenopausal women with osteoporosis at high risk for fracture, defined as a history of osteoporotic fracture, multiple risk factors for fracture, or patients who have failed or are intolerant to other available osteoporosis therapy. In postmenopausal women with osteoporosis, FORTEO reduces the risk of vertebral and nonvertebral fractures.
Increase of Bone Mass in Men with Primary or Hypogonadal Osteoporosis at High Risk for Fracture
FORTEO is indicated to increase bone mass in men with primary or hypogonadal osteoporosis at high risk for fracture, defined as a history of osteoporotic fracture, multiple risk factors for fracture, or patients who have failed or are intolerant to other available osteoporosis therapy.
Treatment of Men and Women with Glucocorticoid-Induced Osteoporosis at High Risk for Fracture
FORTEO is indicated for the treatment of men and women with osteoporosis associated with sustained systemic glucocorticoid therapy (daily dosage equivalent to 5 mg or greater of prednisone) at high risk for fracture, defined as a history of osteoporotic fracture, multiple risk factors for fracture, or patients who have failed or are intolerant to other available osteoporosis therapy.
Treatment of Osteoporosis in Postmenopausal Women
1632 postmenopausal women with osteoporosis were studied for 19 months on Forteo compared to placebo. 90% of subjects had 1 or more vertebral fractures when they entered the study. All patients took calcium and vitamin D.
The rate of new vertebral fractures in the placebo group was 143 per 1,000 vs. 50 in the Forteo group, which was a statistically significant relative risk reduction of 65%. The absolute risk reduction of 9.5% means treatment of 11 women like those in the study for 19 months will result in the prevention of one new vertebral fracture.
The relative risk of peripheral fractures defined for this study as ankle/foot, hip, humerus, pelvis, ribs, wrist, and other sites were significantly reduced in the Forteo group by 53%. Overall, in the placebo group the rate of new peripheral fractures was 55 per 1,000 vs. 26 per 1,000 in the Forteo group.
Forteo’s Effect on Bone Mineral Density (BMD)
FORTEO increased lumbar spine BMD in postmenopausal women with osteoporosis. Statistically significant increases were seen at 3 months and continued throughout the treatment period. The BMD increased 9.7% in the spine, 2.8% in the femoral neck, and 2.6% in the total hip over the 19-month study.
Treatment to Increase Bone Mass in Men with Primary or Hypogonadal Osteoporosis
Forteo was studied in 437 men with either primary (idiopathic) or hypogonadal osteoporosis for 10 months. Statistically significant increases were seen at 3 months and continued throughout the treatment period. The BMD increased 5.9% in the spine, 1.5% in the left femoral neck, which lead to the drug being indicated by the US FDA for these conditions.
Treatment of Men and Women with Glucocorticoid-Induced Osteoporosis
The efficacy of FORTEO for treating glucocorticoid-induced osteoporosis was assessed in 428 people, 19% men, and 81% women with a mean age of 57 years. The average spine T-score was –2.5, indicating the group was osteoporotic. They had all been on 5 mg + of prednisone or its equivalent for at least 3 months. All took calcium and vitamin D during the study, which lasted 18 months. In the Forteo group, the bone density increased 7.2% in the spine, 3.7% in the femoral neck, and 3.6% in the total hip. All these improvements were statistically significant.
Forteo Side Effects
1-34 PTH does have 3 side effects that I encounter in my patients and can confirm but not serious. The first two are mild nausea and dizziness. Both caused by 1-34 PTH raising the blood calcium for several hours after it is taken. Nausea occurs in about 1 in 50 people while dizziness is less common. Taking Forteo at night helps people deal with the symptoms. The body adjusts to this in most cases in a few months at most.
The third side effect is leg cramps. This occurs at night mainly and I think it is due to the muscles, tendons, ligaments, and cartilage needing calcium and magnesium that has been diverted to build bone. My solution is the recommend calcium citrate 315 mg twice daily with one dose at bedtime, vitamin D3 2,000 IU 1 daily, and magnesium oxide 500 mg capsule at bedtime.
None of the other reported side effects and warnings found in the label have been born out by 15 years of clinical experience with the drug in over a million people worldwide. The concerns raised in 2002 did not happen but they remain prominently displayed in the label today. They were actually theoretical concerns proposed by agency scientists based upon biologically plausible serious adverse effects Forteo could have. The fact is their concerns were not born out by reality. The agencies policy is to never change a drug’s label unless the change is needed because information has come to the agencies attention that warrants an increased degree of caution when using the drug.
Warning: Potential Risk Of Osteosarcoma
In male and female rats, teriparatide caused an increase in the incidence of osteosarcoma (a malignant bone tumor) that was dependent on dose and treatment duration. The effect was observed at systemic exposures to teriparatide ranging from 3 to 60 times the exposure in humans given a 20-mcg dose. Because of the uncertain relevance of the rat osteosarcoma finding to humans, prescribe FORTEO® only for patients for whom the potential benefits are considered to outweigh the potential risk. FORTEO should not be prescribed for patients who are at increased baseline risk for osteosarcoma (including those with Paget’s disease of bone or unexplained elevations of alkaline phosphatase, pediatric and young adult patients with open epiphyses, or prior external beam or implant radiation therapy involving the skeleton)
Above is the infamous Black Box Warning that has frightened patients and doctors alike, causing many to eschew Forteo and as a result not receive the fabulous benefits of this biological drug. There were no serious side effects in the registration study presented above or reported in the more than 1,000,000 people who have used 1-34 PTH since the drug was US FDA registered for use in November 2002. Specifically there have been no causes of the bone cancer (osteogenic sarcoma) seen in the rats. What is fascinating about this failure to find even 1 person who developed this rare bone cancer and received 1-34 PTH is that the epidemiology of this disease is well known and by this point in time there should have been about 50 cases of this disease in 1 million people whether they took 1-34 PTH or not. The fact that they have not been able to find any one in the group that took 1-34 PTH with this specific type of cancer is a mystery.
Forteo Label Warnings
The safety and efficacy of FORTEO have not been evaluated beyond 2 years of treatment. Consequently, use of the drug for more than 2 years during a patient’s lifetime is not recommended.
There is no reason why patients who need Forteo for longer than 2 years should not be able to take it. The insurance companies use the above statement to deny approving paying for Forteo beyond 3 years. Many doctors were adhering to the 2-year rule because of their concern about osteosarcoma. The fact that there have not been any cases of that deadly disease in patients exposed to even short courses of Forteo for 15 years has put that concern to rest.
Dr. Woodson’s General Comments on Forteo
1-34 PTH promotes the regrowth of the internal supporting structural elements of bone. It causes the old bone to be removed from the bone and replaces it with significantly more healthy bone that is sturdily anchored to the surrounding bone compartments. In effect 1-34 PTH restores bone health to somewhere in to past causing it to be strong, resilient, stable, connected and teaming with new vigorous osteoblasts and bone attending osteocytes.
Studies show that fracture prevention is apparent in as little as 3 months after beginning 1-34 PTH. After 18 months of therapy, 1-34 PTH significantly decreased the risk of spine and peripheral fractures and increased bone density.
In animal studies, 1-34 PTH caused Fisher 344 rats that are inbred to be high risk for a rare bone cancer to get that cancer, the higher the dose the higher the rate of cancer in the rats.
1-34 PTH is a protein hormone and has to be refrigerated and given by a shot through a tiny needle placed under the skin. You give it yourself and it is easy although almost no one thinks so to begin with. It is surprising to learn that it does not even hurt half the time when giving yourself the shot! I am not kidding. If you go on 1-34 PTH, you will see this is true.
At this point, the drug can only be given for two years because of the rat bone cancer concerns.
One problem with this drug is it costs too much. The retail cost is $2,500/month. Lilly has a co-pay card that helps a lot but it is only available for non-government insured people. Medicare patients pay about $6,000 a year for this drug.
1-34 PTH is truly a treatment that is so effective it might as well be a cure. The effect does not last without help from a follow-on therapy like Prolia to keep and build upon the gains made with 1-34 PTH. The combination of 1-34 PTH followed by long-term Prolia is, in my opinion the very best option available for management of osteoporosis.