A considerable share of MBD patients remains asymptomatic for prolonged periods of time. Here, diagnostic measures like blood sample analyses or radiography carried out for non-related reasons may yield findings consistent with MBD.

On the other hand, MBD diminishes the resistance of osseous structures and patients may present with pathological fractures. In this context, plain radiographic images are usually obtained to visualize fracture lines and displacement, to evaluate the involvement of joints and other anatomical structures. In MBD patients, such images may reveal pronounced anomalies like alterations of bone density. A general reduction or an overall increase of bone mineralization may be observed, for instance, in osteoporosis and osteopetrosis patients, respectively [6] [7]. Alternatively, changes in bone density may be restricted to determined areas. Foci of diminished bone density may be noted in images that also depict areas of enhanced mineralization, e.g., in patients suffering from Paget's disease [8]. Of note, bones of reduced mechanical resistance may succumb to acting forces without breaking. Consequently, MBD patients may present with slowly progressive skeletal deformities hindering their everyday life. Bone pain, secondary arthritis, arthralgia and reduced range of joint motion are commonly described symptoms.

Because the skeleton plays a primordial role in calcium and phosphate homeostasis, MBD patients frequently suffer from alterations of serum electrolyte levels and corresponding clinical symptoms. In otherwise asymptomatic patients, hypocalcemia, hypercalcemia, hypophosphatemia, and hyperphosphatemia may constitute first indicators of MBD.

• Anemia

  The only hematological abnormality was moderate anemia, which prompted bone marrow studies leading to a diagnosis of acute lymphoblastic leukemia (ALL). [ncbi.nlm.nih.gov]

  Fanconi's anemia or associated with a viral infection with parvo virus. Iron deficiency anemias Iron deficiency anemias lead to the formation of deformed and smaller RBCs released from the marrow. [news-medical.net]

  Enzymatic amplification of β-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science 1985; 230: 1350-4. PMID: 2999980. 10. Donis-Keller H, et al. A genetic linkage map of the human genome. [molcom.jp]

• Lymphadenopathy

  He had no lymphadenopathy or organomegaly. The only hematological abnormality was moderate anemia, which prompted bone marrow studies leading to a diagnosis of acute lymphoblastic leukemia (ALL). [ncbi.nlm.nih.gov]

• Tooth Loss

  We describe a new familial metabolic bone disease characterized by expanding hyperostotic long bones, early onset deafness, premature tooth loss, and episodic hypercalcemia. [ncbi.nlm.nih.gov]

• Ulcer

  Osteomalacia and osteoporosis are commonly observed in patients who have had partial gastric resections for treatment of peptic ulcer disease. [ncbi.nlm.nih.gov]

  Generalised weakness, urolithiasis, peptic ulcer disease, pancreatitis, bone and joint pain. 40% have skeletal abnormality on XR. [radnotes.co.nz]

• Sparse Hair

  Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive disorder characterized by poikiloderma, small stature, sparse hair, skeletal abnormalities, increased risk of osteosarcoma, and decreased bone mass. [ncbi.nlm.nih.gov]

• Distractibility

  In addition, six femora in three patients were subsequently lengthened by distraction osteogenesis. The mean follow-up was 60 months (18 to 120). [ncbi.nlm.nih.gov]

  Banana/chalkstick fractures – transverse distraction insufficiency fractures on covexity of deformed bone. Shephard’s crook deformity – varus proximal femur. Overingestion of fluoride, vitamin A or D. [radnotes.co.nz]

At first glance, pathological fractures may not be distinguished from traumatic lesions. Thus, it is important to carry out additional studies to confirm whether the patient suffers from an underlying disorder rendering them prone to bone fractures, particularly if there is no apparent relation between traumatic insult and fracture, or if patients repeatedly present with fractures. Anamnestic data should be considered when deciding to undertake either of the following measures:

• Laboratory analyses of blood samples to determine serum electrolyte levels and additional parameters
• Bone mineral density measurements [9]
• Genetic screening to identify hereditary MBD
• Scintigraphy [10]
• Bone biopsy and histopathological examination of obtained specimens

This also applies in the case of other symptoms or incidental findings consistent with MBD.

Metabolic bone disease (MBD) is a general term that may refer to distinct entities associated with disturbances of anabolic and catabolic processes, bone homeostasis and remodeling. Even though an exhaustive list of MBD is not available currently [1] [2], the following pathologies can be named exemplary:

• Hypophosphatasia, a hereditary disorder resulting in reduced activity of alkaline phosphatase and insufficient bone mineralization.
• Osteopetrosis, a hereditary disease associated with impaired osteoclastic bone resorption.
• Osteoporosis, a common MBD caused by imbalances between bone formation and bone resorption.
• Paget's disease (osteitis deformans), an MBD of unknown etiology characterized by focal disturbances of osteoblast and osteoclast activity.
• Rickets and osteomalacia, most commonly caused by vitamin D deficiency and associated with insufficient bone mineralization.

Bone metabolism is highly dependent on endocrinological factors such as thyroid, parathyroid, adrenal and gonadal hormone release and on the availability of electrolytes [3]. In this context, diseases like hypo-/hyperparathyroidism, Cushing's disease [4], celiac disease, inflammatory bowel disease [5], and renal tubular acidosis may provoke secondary MBD.

MBD treatment depends on the underlying disorder. In general, physical therapy is indicated to stimulate muscle gain. This approach is usually complemented with dietary adjustments and medication. Some conditions may also require surgical management.

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