Camurati-Engelmann Disease (CED) is a rare sclerosing bone disease, sometimes associated delayed puberty. The treatment effect of glucocorticoid and angiotensin II receptor blocker (ARB) in bone health and puberty development remain unclear. We report a case of an 18-year-old girl who presented for a history of an enlarged head, pain of lower limbs, and no menstrual onset or breast development. Radiographs revealed thickening of skull and cortices in the diaphysis but sparse bone trabeculae in the spine and metaphysis. Sanger sequencing detected a mutation of c. 652C>T (p. R218C) in the gene TGFB1 and confirmed the diagnosis of CED. After treatment of a medium-to-small dosage of prednisone and losartan for 28 months, we observed improvement of bone mass in spine and hip and body fat mass and found initiation of puberty development. By a systemic review of current treatment strategies in patients with CED, we found that most cases reported relief of bone pain with treatment of glucocorticoid or ARB, but none has reported the outcome of hypogonadotropic hypogonadism. We propose that long-term use of glucocorticoid combined with ARB may inhibit the activation of TGFβ1 in CED, improve adipogenesis, and thus initiate puberty development and improve the bone mass in spine and hip.

UNASSIGNED: The treatment of Camurati-Engelmann disease (CED) involves the use of glucocorticoids, analgesics, and bisphosphonates; experience with the use of losartan is limited. Our objective was to describe the case of a patient diagnosed with CED whose symptoms remained refractory while on steroids and bisphosphonates and who was successfully treated with losartan.
UNASSIGNED: A 27-year-old woman presented with bone pain involving her extremities and large joints for 1 year. Clinical examination revealed bone tenderness and proximal myopathy with elevated C-terminal peptide of type 1 collagen (1617 pg/mL; normal range, 137-573 pg/mL) and N-terminal propeptide of type 1 procollagen levels (163 ng/mL; normal range, 5.1-58.3 ng/mL). Calcium (9.4 mg/dL; normal range, 8.3-10.4 mg/dL), phosphate (3.4 mg/dL; normal range, 2.5-4.5 mg/dL), and parathyroid hormone (62 pg/mL; normal range, 8-80 pg/mL) levels were within the normal range. Radiographs showed hyperostosis involving the diaphyseal region of long bones of the lower and upper limbs, and a provisional diagnosis of CED was made. She was treated with prednisolone, 30 mg daily, with which she reported some improvement. As exogenous Cushing syndrome had developed in her because of prednisolone, its dose was tapered. Subsequently, her bone pain worsened. Thereafter, she was initiated on oral alendronate. Due to persistent pain, losartan was added, after which she had marked decrease in bone pain with a reduction in the C-terminal peptide of type 1 collagen (375 pg/mL) and N-terminal propeptide of type 1 procollagen (50 ng/mL) levels.
UNASSIGNED: Occasionally, CED presents therapeutic challenges, and when its symptoms remain refractory to conventional doses of steroids and bisphosphonates, other options may be needed. The abovementioned patient was initiated on losartan, which acts by downregulation of transforming growth factor β1, leading to the reduction in pain.
UNASSIGNED: Losartan downregulates transforming growth factor β1 and may be offered as a steroid-sparing option in individuals diagnosed with CED if symptoms remain refractory to conventional treatment.

UNASSIGNED: Camurati-Engelmann disease (CED) is a rare bone dysplasia characterized by diffuse diaphyseal osteosclerosis. Skull base involvement in CED can result in hypopituitarism but is seldom reported. Our objective was to report a patient with acquired hypopituitarism due to CED and assess the management challenges.
UNASSIGNED: A 20-year-old boy presented with lower limb pain. He had walking difficulty in childhood, which was diagnosed as CED and managed with prednisolone. He later discontinued treatment and was lost to follow-up. Current re-evaluation showed short stature (-3.6 standard deviation), low weight (-4.3 standard deviation), and delayed puberty with delayed bone age (13 years). He was found to have secondary hypogonadism (luteinizing hormone level, 0.1 mIU/mL [1.7-8.6 mIU/mL]; follicle-stimulating hormone level, 1.0 mIU/mL [1.5-12.4 mIU/mL]; and testosterone level, 0.087 nmol/L [9-27 nmol/L]), growth hormone deficiency (low insulin-like growth factor I level, 120 ng/mL [226-903 ng/mL] and peak growth hormone level of 7 ng/mL on insulin-induced hypoglycemia), and secondary hypocortisolism (cortisol level, 105 nmol/L [170-550 nmol/L] and adrenocorticotropic hormone level, 6 pg/mL [5-65 pg/mL]). Serum prolactin level was normal (8.3 ng/mL [5-20 ng/mL]), and he was euthyroid on levothyroxine replacement. Magnetic resonance imaging revealed a partially empty sella. Sanger sequencing revealed a missense mutation (p.R218C/c.652C>T) in exon 4 of the TGFβ1 gene. The patient was treated with zoledronate, losartan, and oral prednisolone and continued on levothyroxine and testosterone replacement, which resulted in symptomatic improvement.
UNASSIGNED: The index case manifested severe CED requiring multimodality therapy. Later, he developed combined pituitary hormone deficiencies, which were managed with thyroid and gonadal hormone replacement with the continuation of glucocorticoids. The partial efficacy of bisphosphonates in CED has been reported in the literature.
UNASSIGNED: Skull base involvement in CED can lead to structural and functional hypopituitarism as a result of intracranial hypertension.

Camurati-Engelmann disease (CED) is a rare autosomal-dominant skeletal dysplasia caused by mutations in the transforming growth factor-β1 (TGFB1) gene. In this study, a retrospective review of patients with CED evaluated at Peking Union Medical College Hospital in Beijing, China, between November 30, 2000 and November 30, 2020 was conducted. Data including demographic data, manifestations, and examination results were characterized. Furthermore, bone geometry, density, and microarchitecture were assessed and bone strength was estimated by HR-pQCT. Results showed the median age at onset was 2.5 years. Common manifestations included pain in the lower limbs (94%, 17/18), abnormal gait (89%, 16/18), genu valgum (89%, 16/18), reduced subcutaneous fat (78%, 14/18), delayed puberty (73%, 8/11), muscle weakness (67%, 12/18), hearing loss (39%, 7/18), hepatosplenomegaly (39%, 7/18), exophthalmos or impaired vision or visual field defect (33%, 6/18), and anemia (33%, 7/18). Twenty-five percent (4/16) of patients had short stature. Serum level of alkaline phosphatase was elevated in 41% (7/17) of patients whereas beta-C-terminal telopeptide was elevated in 91% of patients (10/11). Among 12 patients, the Z-scores of two patients were greater than 2.5 at the femur neck and the Z-scores of five patients were lower than -2.5 at the femur neck and/or lumbar spine. HR-pQCT results showed lower volumetric BMD (vBMD), altered bone microstructure and lower estimated bone strength at the distal radius and tibia in patients with CED compared with controls. In addition, total volume bone mineral density and cortical volumetric bone mineral density at the radius were negatively correlated with age in patients with CED, but positively correlated with age in controls. In conclusion, the largest case series of CED with characterized clinical features in a Chinese population was reported here. In addition, HR-pQCT was used to investigate bone microstructure at the distal radius and tibia in nine patients with CED, and the alteration of bone density, microstructure, and strength was shown for the first time. © 2021 American Society for Bone and Mineral Research (ASBMR).

Camurati-Engelmann disease (CED) is a rare, progressive diaphyseal dysplasia characterized as diaphyseal hyperostosis and sclerosis of the long bones. Corticosteroids, bisphosphonates, and losartan have been reported to be effective systemic medications used to reduce CED symptoms. There are no reports of osteoblastoma in patients with CED, and osteoblastoma in the distal radius is rare. We present a patient diagnosed with CED, based on radiological and histological examinations, at 11 years old. At 22 years old, she experienced severe pain in her right forearm and was treated with bisphosphonate, losartan, and prednisolone; however, the pain continued. An expansive and sclerotic lesion at the distal radius was observed on radiography. A follow-up plain radiograph indicated that the lesion was growing. Fluorodeoxyglucose positron emission tomography revealed solitary, intense radiotracer uptake, and a biopsy and surgical resection were performed due to suspected malignancy. Pathologic analysis showed anastomosing bony trabeculae rimmed by osteoblasts observed in a loose fibrovascular stroma. The lesion was diagnosed as an osteoblastoma. Following bone excision and artificial bone grafting, the patient\'s severe pain almost completely disappeared. At final follow-up, no evidence of osteoblastoma recurrence was noted. To our knowledge, this is the first case report of osteoblastoma arising in a patient with CED. Bone excision and artificial bone grafting may be a treatment option for local symptomatic osteoblastoma in patients with CED.

Camurati-Engelmann disease or progressive diaphyseal dysplasia is a rare autosomal dominant sclerosing bone dysplasia. Mainly the skull and the diaphyses of the long tubular bones are affected. Clinically, the patients suffer from bone pain, easy fatigability, and decreased muscle mass and weakness in the proximal parts of the lower limbs resulting in gait disturbances. The disease-causing mutations are located within the TGFβ-1 gene and expected to or thought to disrupt the binding between TGFβ1 and its latency-associated peptide resulting in an increased signaling of the pathway and subsequently accelerated bone turnover. In preclinical studies, it was shown that targeting the type I receptor ameliorates the high bone turnover. In patients, treatment options are currently mostly limited to corticosteroids that may relieve the pain, and improve the muscle weakness and fatigue. In this review, the clinical and radiological characteristics as well as the molecular genetics of this condition are discussed.

Camurati-Engelmann (CE) is a very rare disease affecting one in every million persons worldwide. It is characterized by an enlargement of long bones. We aimed to assess bone characteristics in three siblings with different tools. Even if there was an excess of bone density, quality seemed to be deteriorated.
CE disease is a rare monogenic disorder affecting approximately one in every million persons worldwide. It is mainly characterized by a progressive hyperostosis of the periosteum and endosteum of the diaphysis of long bones. Limited data are available about bone characteristics in these patients. In three siblings with CE disease, we aimed to assess bone mineral density (BMD) and trabecular bone score (TBS) by dual-energy X-ray absorptiometry (DXA) and material characteristics at tissue level using bone impact reference point indentation.
Clinical data were collected and a general laboratory workup was performed. At the lumbar spine and hip, BMD and TBS were measured using DXA imaging. Bone material strength index (BMSi) was measured by bone impact microindentation using an Osteoprobe instrument.
All three cases had densitometric values consistent with high bone mass (sum of Z-score at the lumbar spine and hip > 4). Hip BMD was extremely high in all three siblings at both total hip and femoral neck, while at the lumbar spine, two of them had normal values but the third again had very high BMD. TBS values were in the normal range. In contrast, BMSi measurements were at low or very low levels, compared with normal controls.
Despite strikingly increased BMD and normal microarchitecture, BMSi is affected in patients with CE. Microindentation could be an appropriate tool for assessing bone fragility in these patients. Bone disease in this group of patients requires further study to better understand the underlying regulatory mechanisms and their alterations.

Engelmann-Camurati disease (ECD) is a rare bone disorder characterized by autosomal dominant inheritance. It usually presents in early childhood and is associated with symmetrical diaphyseal sclerosis. We report a 20-year-old female with scintigraphic findings characteristic of ECD. She was treated with corticosteroids and showed marked clinical improvement.