A 26-Year-Old Woman Who Uses a Walking Cane Because of Pain

Ricardo Correa, MD; Gauri Behari, MD


September 13, 2019

Data on treatment of hypophosphatasia in the adult population are limited. Hypophosphatasia has a significantly negative impact on quality of life. Almost all adult patients report chronic pain in bone, joints, and muscles; a large majority require daily use of analgesic drugs.[10] Therefore, pain management is a mainstay of therapy. A combination of physiotherapy, occupational therapy, and chronic pain management is most effective.[11]

Enzyme replacement therapy using bone-targeting recombinant alkaline phosphatase or asfotase alfa has been used to treat infants, children, and some adults with hypophosphatasia. A long-term study of asfotase alfa demonstrated improvement of bone mineralization, respiratory function, and survival rate in 37 patients with hypophosphatasia compared with 48 historical controls.[12] Suggested indications for treatment of hypophosphatasia in adults with asfotase alfa include history of childhood involvement (< 18 y), and one or more of the following:

  • Musculoskeletal pain requiring prescription pain medications

  • Disabling polyarthropathy or chondrocalcinosis

  • Major low trauma fracture attributable to hypophosphatasia (eg, spine, hip, humerus)

  • Delayed or incomplete fracture healing or fracture nonunion

  • Repeated episodes of orthopedic surgery for complications of hypophosphatasia

  • Disabling functional impairment affecting mobility, gait, and activities of daily living

  • Low bone mineral density on dual-energy x-ray absorptiometry

  • Radiologic evidence of nephrocalcinosis

Currently, no guidelines are available for selecting adult patients for treatment, evaluating results of treatment, or determining optimal duration of hypophosphatasia treatment.[11,12,13,14] Teriparatide has also been used in patients with hypophosphatasia. In a study of 10 adult patients, hypophosphatasia was treated with teriparatide to increase osteoblast production of ALP.[15] Effects of treatment on bone mineral density varied; however, the study found improvements in pain, mobility, and fracture repair in some cases.

In another study, eight adult patients were treated with anti-sclerostin monoclonal antibody.[16] Treatment for 29 weeks increased bone formation markers and transiently decreased C-telopeptide. Lumbar spine bone mineral density showed a mean increase of 3.9% at the end of the study.

A key point in management is that treatment with antiresorptive agents (eg, bisphosphonates) is contraindicated because they may further lower the ALP level and are harmful in patients with hypophosphatasia. Although this disease is physical, several studies underline that mental and emotional health are affected in adult patients with hypophosphatasia.[6,17]


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