The forms of Miller’s disease are subdivided into hypocalcaemic and hypophosphataemic rickets as well as hypophosphatasia.
Miller’s disease is a metabolic bone disease in which sufficient bone is present but it is inadequately mineralised.
Miller’s disease with reduced serum calcium is usually caused by vitamin D deficiency. This is often accompanied by secondary hyperparathyroidism. The most frequent causes of vitamin D deficiency or the reduced effect of vitamin D are:
- Lack of sunlight
- Ageing skin (from the age of 60, the skin virtually no longer metabolises vitamin D)
- Cosmetics containing sun protection factor
- Position of the sun too low (spring, winter, autumn)
- Defective hepatic metabolisation
- Administration of anti-epileptic drugs
- Renal insufficiency
- 1-alpha-hydroxylase genetic defects
- Vitamin D receptor defects
Miller’s disease with low serum phosphate usually involves a PHEX/FGF23 metabolism disorder. These diseases are often genetically related or are triggered by a tumour disease.
The most frequent form is phosphate diabetes [(X-linked hypophosphataemic rachitis (XLH)]. These patients have usually been suffering from bone deviations since childhood; the previously common therapy with phosphate and vitamin D is poorly tolerated. Now, however, we have an FGF23 antibody, burosumab (Crysvita®), which has led to considerably better patient management. Prof. Wüster’s hormone & metabolism centre in Mainz is a centre for treating XLH patients with this new drug.
Hypophosphatasia (HPP) is a genetic disease of the alkaline phosphatase that goes hand-in-hand with multiple clinical symptoms. Patients can suffer muscular complaints and are often misdiagnosed as having fibromyalgia or, previously, soft tissue rheumatism. The Prof. Wüster hormone & metabolism centre in Mainz is one of the osteological centres that deals intensively with this disease and its therapy. Throughout Germany, Mainz is among the institutes that treat the highest number patients with life-saving enzyme replacement therapy.
Tooth loss and poor teeth as well as bone fractures during childhood are typical examples of HPP and indications for therapy. Stress fractures are very often caused by HPP. Causal therapy is available in the form of enzyme replacement therapy with recombinant alkaline phosphatase = asfotase alfa (Strensiq®).