Treatment of adult hypophosphatasia with teriparatide.

Abstract

OBJECTIVE:

To describe the effects of 24 months of teriparatide therapy in an adult with hypophosphatasia, which thus far has no established medical treatment.

METHODS:

A 75-year-old woman with hypophosphatasia was treated with ergocalciferol and calcium supplements for 2 years. She had sustained multiple spontaneous and low-trauma fractures since she was 10 years old. Baseline biochemical values (and reference ranges) were as follows: serum total alkaline phosphatase ranged from 14 to 17 U/L (30 to 110), bone-specific alkaline phosphatase (BSALP) was 5 U/L (14 to 43), serum phosphorus was elevated at 5.4 mg/dL (2.6 to 4.4), and pyridoxal 5'-phosphate was high at 250 ng/mL (5 to 30). At baseline, she had mild secondary hyperparathyroidism (intact parathyroid hormone, 76 pg/mL; reference range, 10 to 65), which was corrected by the calcium supplementation and vitamin D therapy. Dual-energy x-ray absorptiometry (DXA) scanning in 2003 showed L1-L4 bone mineral density (BMD) of 0.786 g/cm2, T score of -3.3, and Z score of -1.7; DXA also showed femoral neck BMD of 0.740 g/cm2, T score of -2.5, and Z score of -0.5. During walking, the patient sustained a low-trauma fracture in a metatarsal. Teriparatide, synthetic parathyroid hormone(1-34), in a dosage of 20 microg subcutaneously was given daily from April 2004 until June 2006.

RESULTS:

After about 1.5 years of teriparatide therapy, BSALP reached the lower end of the reference range at 16 U/L, and after 24 months of continuous teriparatide treatment, both serum total alkaline phosphatase and BSALP normalized at 30 U/L and 18 U/L, respectively. Pyridoxal 5'-phosphate declined from a baseline of 250 to 188 ng/mL after 17 months of treatment. Urinary N-telopeptide increased from a baseline of <6 to 19 after 17 months and to 70 bone collagen equivalents/mmol creatinine after 24 months of anabolic therapy. Repeated DXA scanning showed a substantial improvement in lumbar spine BMD and stability in hip BMD. The patient experienced no clinical fractures or adverse events during teriparatide therapy.

CONCLUSION:

In one woman with adult hypophosphatasia, 2 years of teriparatide treatment improved biochemical markers of bone remodeling and increased skeletal mineralization. Teriparatide may prove to be a viable treatment for adult hypophosphatasia; thus, this intervention warrants further evaluation.

• Authors: Pauline M Camacho, Stephanie Painter, Ruth Kadanoff
• Journal: Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists (Endocr Pract) Vol. 14 Issue 2 Pg. 204-8 (Mar 2008) ISSN: 1934-2403 [Electronic] United States
• PMID: 18308659 (Publication Type: Case Reports, Journal Article)

Chemical References

• Bone Density Conservation Agents
• Collagen Type I
• Peptides
• collagen type I trimeric cross-linked peptide
• Teriparatide
• Vitamin D
• Phosphorus
• Alkaline Phosphatase
• Calcium

Topics

• Absorptiometry, Photon
• Aged
• Alkaline Phosphatase (blood)
• Bone Density (drug effects)
• Bone Density Conservation Agents (therapeutic use)
• Calcium (therapeutic use)
• Collagen Type I (urine)
• Female
• Humans
• Hyperparathyroidism (drug therapy)
• Hypophosphatasia (blood, drug therapy, urine)
• Peptides (urine)
• Phosphorus (blood)
• Teriparatide (therapeutic use)
• Treatment Outcome
• Vitamin D (therapeutic use)