Significant Improvement of Clinical Symptoms, Bone Lesions, and Bone Turnover after Long-Term Zoledronic Acid Treatment in Patients with a Severe Form of Camurati-Engelmann Disease

Abstract

Camurati-Engelmann disease (CED) is an ultrarare autosomal dominant bone dysplasia. Cortical thickening of the diaphyses of the long bones with narrowing of the medullary cavity are associated with bone pain, waddling gait, muscular weakness, easy fatigability, and a marfanoid body habitus. There is no specific treatment for CED. Nonsteroidal anti-inflammatory drugs or glucocorticoids are ineffective in improving bone lesions. A family with a mild to severe form of CED is described. Two patients received long-term bisphosphonate treatment: the 19-year-old female proband was treated with zoledronic acid for 2.2 years; the 4-year-old male proband was treated with neridronic acid for 16 months and with zoledronic acid for an additional 18 months. In both probands, zoledronic acid treatment significantly improved the clinical symptoms, bone lesions, ambulation, and body habitus. Before treatment, both probands showed a marked increase in serum levels of osteocalcin, procollagen type I N-terminal propeptide, and cross-linked carboxyterminal telopeptide of type I collagen, reflecting an increased bone turnover. Bone marker levels returned to their normal values during treatment. Zoledronic acid treatment may be an important therapeutic option in patients with severe CED. Biochemical markers of bone turnover could be considered as surrogate indexes of CED activity.

Clinical Characteristics And Identification of Novel TGF-β1 Mutation In Three Unrelated Chinese Families With Progressive Diaphyseal Dysplasia

“…The above variant clinical manifestations may be closely related to post-translational modi cation and other regulatory factors, and mechanical stimulation may also play a partial role [9,20]. Previous study in large pedigrees had described a tendency of PDD to occur earlier and more severe in the younger generations [7,11,12], which was genetically named "anticipation". In the present study, family 1 and family3 were consistent with the ndings of the above.…”

“…However, our department had ever demonstrated the bene cial utility of both alendronate and zoledronate in two male patients with PDD in 2019 [6]. Intriguingly, it seemed that men tended to gain better therapeutic effects better than women [7,8,26,28,29]. Whether sex hormones play a role in the therapeutic response of bisphosphonates to diseases is unknown, which is also one of the research contents we need to study in the future.…”

“…Some cases have systemic manifestations or like some kind of syndromes, accompanied with anemia, leukopenia and hepatosplenomegaly for instance [5]. Since PDD is a kind of rare disease, to date, there are altogether 300 cases with PDD have been reported over the world [4,[6][7][8][9][10][11][12]. Therefore, the diagnosis of PDD is a great challenge for clinicians owing to its rarity and extensive phenotypic variations.…”

Correction of Orbital Deformity in Camurati-Engelmann Disease with PEEK Lateral Wall Implants

“…Some studies have demonstrated reduced biochemical markers of bone turnover and improved symptoms, with other studies demonstrating no effect. 17,18 Surgical options for correction of raised intercranial pressure and papilledema include cranial volume expansion with craniectomy and titanium mesh cranioplasty. 19 Symptomatic skull base involvement may require cranial nerve decompression surgery.…”

Insights Into Management of Camurati-Engelmann Disease: A Case Series of Three Siblings

“…Bisphosphonate therapy has been attempted due to the presence of increased markers of bone turnover (osteocalcin, procollagen type 1 N-terminal propeptide, and cross-linked carboxyterminal telopeptide of type 1 collagen) found in patients with CED. Zoledronic acid has been shown to normalize these markers of bone turnover and result in pain improvement in some patients [15]. Nevertheless, its use is disputed as there are reports of worsening pain in other patients [12].…”