Both radiologic and clinical findings may prompt a suspicion for OM. Thus, the disease may be diagnosed in patients undergoing diagnostic imaging for any other reason, or in individuals that present with characteristic symptoms. Generalized bone pain as well as symmetrical bone pain localized to vertebral spine, pelvis and thighbones are frequent causes of presentation to health care givers. Arms and ribs may be affected during later stages of the disease. Bone pain may be accompanied by fatigue, proximal muscle weakness and gait disturbances. Patients often report to have difficulties to rise from a sitting or prone position, or to climb stairs. In other cases, they present with (recurrent) pathological fractures.

In plain radiographic images, reduction of bone density (osteopenia) and Looser zones (pseudofractures) are frequently detected [9]. Vertebrae and pelvic bones may be compressed, and in severe cases, the patient's stature may progressively diminish. Alterations of spine curvature may be noted.

• Fatigue

  A 43-year-old male presented with fatigue, low back pain, and morning stiffness. He had a 6-year history of seronegative spondyloarthropathy associated with Crohn's disease. [ncbi.nlm.nih.gov]

  We ask about general symptoms (anxious mood, depressed mood, fatigue, pain, and stress) regardless of condition. Last updated: January 31, 2019 [patientslikeme.com]

  Supplementation and sun exposure Muskuloskeletal health Heart health Cancer Autoimmune conditions Mental health Developmental disorders Pregnancy and fertility Aging Fitness and exercise Gastrointestinal health Asthma Infections Everyday aliments: fatigue [vitamindcouncil.org]

  These non-specific aches and pains in the bones and muscles are often misdiagnosed as fibromyalgia or chronic fatigue syndrome," writes Dr. Michael Holick, one of the world's foremost authorities on vitamin D. [naturalnews.com]

• Swelling

  We detected a swelling in her right groin and suspected tumour induced osteomalacia. Resection of the tumour led to reversal of metabolic bone disease. Patient became ambulatory within 6 weeks of tumour resection. [ncbi.nlm.nih.gov]

  Other signs include costochondral swelling (rachitic rosary), spinal curvature and signs of hypocalcaemia (eg, tetany, carpopedal spasm). [patient.info]

  • Rachitic rosary • Swelling of the costo-chondral junction • Harrison’s groove • Lateral indentation of the chest wall at the site of attachment of diaphragm because the patients lack the mineralized calcium in their bones necessary to harden them; [slideshare.net]

• Pathologist

  Dietary Increased phosphate loss Vitamin D resistant rickets Fanconi syndrome See under Renal tubular disorders Drug induced, especially Bisphosphonates Fluoride Antacid abuse Toxic Bone biopsy with measurement of toxic metal; consult pathologist. [rcpa.edu.au]

  When biopsy is necessary and if local pathologist is not familiar with the preparation of an undecalcified, plastic-embedded, bone specimen to identify defective mineralization, the best solution is to refer the patient to a bone histomorphometry center [endocrinologyadvisor.com]

  Many of these tumors appear to have been largely misunderstood, ignored, or unknown by most pathologists and clinicians. [scielo.br]

• Pallor

  On examination, there are skeletal deformities of both upper and lower limbs with marked bowing General examination shows pallor, otherwise there are no other signs.The abdomen is distended, otherwise systemic examination is normal. SOEPEL 4. [slideshare.net]

• Intestinal Disease

  The very low serum calcium values may represent further calcium malabsorption as a consequence of the intestinal disease, as well as the rapid shift of calcium into the mineralizing skeleton. [endotext.org]

  Patients with intestinal disease, such as cystic fibrosis, celiac sprue and bypass surgery for obesity, are prone to vitamin D deficiency. Even if they take supplements, the vitamin D is not absorbed or is broken down too quickly. [courses.washington.edu]

• Failure to Thrive

  Rickets Clinical feature General Failure to thrive Apathetic, listless, irritable Shorter, lower body weight and anemic Excessive sweating particularly at hand & face 18. [slideshare.net]

• Bone Pain

  Definition (MSH) Disorder caused by an interruption of the mineralization of organic bone matrix leading to bone softening, bone pain, and weakness. [fpnotebook.com]

  Adults can experience similar symptoms such as bone pain, muscle weakness and fragile bones that are more prone to fractures. In adults, these symptoms are known as osteomalacia. [nhs.uk]

  A 64-year-old man suffering polyarthralgia and bone pain was referred to our hospital. Renal dysfunction, hypophosphatemia and increased levels of bone alkaline phosphatase were found. [ncbi.nlm.nih.gov]

• Osteoporosis

  Osteoporosis Definition of osteoporosis: Osteoporosis is a bone disease which characterized by low bone mass as result of body loses too much bone and makes too little bone. [aclr.com.es]

  Define and contrast osteoporosis and osteomalacia. Both osteoporosis and osteomalacia can cause weak bones. In osteoporosis, there is decreased bone mass with a normal ratio of mineral to matrix. [orthopaedicsone.com]

  Osteoporosis is much more common than osteomalacia in the US. The two disorders may coexist, and their clinical expression is similar; moreover, mild to moderate vitamin D deficiency can occur in osteoporosis. [msdmanuals.com]

• Bone Disorder

  Osteomalacia is a metabolic bone disorder characterized by impaired mineralization of bone matrix. Symptoms of osteomalacia can be confused with other conditions such as spondyloarthropathy, polymyalgia rheumatica, polymyositis, and fibromyalgia. [ncbi.nlm.nih.gov]

  This is particularly true if your bone disorder is not seen in conjunction with another serious medical condition. [disability-benefits-help.org]

  Identification of the underlying disorder is of utmost importance to treat the disease. The outcome largely depends on the primary disorder and the extent of bone deformations, if present. [symptoma.com]

• Proximal Muscle Weakness

  Proximal muscle weakness, spinal tenderness to percussion, pseudofractures, and skeletal deformities are found commonly. [bestpractice.bmj.com]

  All had generalized bone pain and tenderness, muscle weakness, stooping posture, difficulty walking, and waddling gait due to severe proximal muscle weakness for a period of 2 to 5 years. [ncbi.nlm.nih.gov]

  muscle weakness, concurrent severe vitamin D deficiency (17.1 nmol/l), hypophosphatemia (0.40 mmol/l) and a raised alkaline phosphatase (720 u/l). [academic.oup.com]

  […] pain fractures of long bones, ribs and vertebrae proximal muscle weakness weakness fatigue Physical exam inspection waddling gait from hip pain and thigh weakness difficulty rising from chair and climbing stairs Imaging Radiographs findings Bone scan [orthobullets.com]

• Genu Valgum

  Bowing of the legs (genu varum) is typical, but knock knees (genu valgum) can also occur. [patient.info]

  The most characteristic findings include: growth retardation, deformities in upper and lower limbs (genu varum or genu valgum) generally noted when the infant begins to creep or to walk, metaphyseal widening, palpable enlargement of the costochondral [scielo.br]

• Lethargy

  In addition, one may experience… Fractured bones due to minimal trauma Lethargy Stiffness Muscle Weakness: Muscle weakness tends to affect the thighs and the muscles in the shoulders and main core of the body. [algaecal.com]

  Osteomalacia Mildly affected patients may present with widespread bone pain and tenderness (especially low back pain and in the hips), proximal muscle weakness and lethargy. [patient.info]

• Abnormal Gait

  Snapshot A 6-year-old boy is brought to his pediatrician by his parents due to poor growth, weakness, and abnormal gait. On physical exam, there is bowing of the legs and tenderness upon palpation of the lower extremity. [step2.medbullets.com]

Symptoms largely resemble those of the more common osteoporosis and neither anamnestic data nor results of physical examination allow for a clear distinction between both bone disorders. Laboratory analyses of blood samples are very helpful to this end. Alterations of parameters like serum calcium, phosphate, pre-vitamin D, vitamin D, PTH, urea and creatinine may indicate hypocalcemia or hypophosphatemia, vitamin D deficiency, hyperparathyroidism and renal insufficiency, and thus argue for OM. Alkaline phosphatase levels are elevated in all forms of OM and osteoporosis; this parameter is highly sensitive but little specific and does neither permit to infer about the underlying disease.

In most cases, vitamin D deficiency accounts for OM. This condition is associated with hypophosphatemia, reduced concentrations of pre-vitamin D and vitamin D, and possibly hypocalcemia, whereby the latter is not an exclusion criterion. In case of hypocalcemia, PTH concentrations may be elevated and the patient may be diagnosed with secondary hyperparathyroidism.

If these measurements don't permit a definite diagnosis, calcium and phosphate excretion should be revised by analysis of a 24-hour urine sample. In case of confirmed kidney disease, the respective workup should be realized: Renal sonography and pyelography are valuable techniques, but the therapeutic approach of choice largely depends on prior findings.

• Nephrolithiasis

  […] antacid-induced osteomalacia osteomalacia in which the combination of low dietary phosphorus intake and chronic excessive consumption of aluminum hydroxide–containing antacids has led to phosphate depletion; characteristics include hypophosphatemia, nephrolithiasis [medical-dictionary.thefreedictionary.com]

  Osteomalacia Clinical feature Long standing case sign of secondary hyperparathyroidism • Depression • Polyuria • Increased thirst • Constipation • Nephrolithiasis • ?Peptic Ulcer Disease 38. Osteomalacia X- ray • Looser zone 39. [slideshare.net]

• Phosphate Decreased

  He had multiple stress fractures, low serum phosphate, decreased renal tubular reabsorption of phosphate, and normal PTH and FGF23, indicating adult onset hypophosphatemic osteomalacia. [ncbi.nlm.nih.gov]

  PTH raises calcium concentration but also increases renal clearance of phosphate. When phosphate decreases below a critical level, mineralization cannot proceed normally. [wikilectures.eu]

  PTH raises calcium concentration but also increases renal clearance of phosphate. Once phosphate decreases lower than a critical level, mineralization cannot proceed normally as in Figure 5 [ 20 ]. Figure 5: Pathophysiology of osteomalacia. [aclr.com.es]

• Alkaline Phosphatase Increased

  Alkaline phosphatase increased over time (linear component, r 2 = 0.46, F 1,28 = 23.9, p = 0.000037). Figure 2 Serum 25-hydroxyvitamin D levels in historical controls and psychiatric inpatients. [bmcresnotes.biomedcentral.com]

Because OM occurs secondary to an underlying disease, causative treatment of OM consists in curing the respective primary disorder.

• Since vitamin D deficiency is the main trigger of OM, such treatment commonly consists in adjusting dietary habits and daily intakes of vitamin D, calcium and phosphate.
• Dietary supplementation of deficient nutrients is also indicated in case of chronic gastrointestinal disorders like celiac disease. Dose increases may be necessary to assure absorption of adequate quantities of nutrients. Additional, specific measures should be considered.
• Secondary hyperparathyroidism generally remits as soon as serum calcium levels normalize.
• In case of primary hyperparathyroidism, a condition provoked by neoplasms of the parathyroid glands, surgical resection of tumors may be required.
• If an OM patient is diagnosed with primary kidney disease, it should be adequately treated. Here, dietary supplementation of phosphate, calcium and vitamin D may be necessary.
• Drug-induced OM requires the readjustment of therapy of comorbidities.

Improvement of OM-associated symptoms may be expected a few weeks after the initiation of an adequate treatment. The above mentioned blood parameters should be evaluated periodically after starting therapy. Additionally, bone mineral density tests should be performed to monitor response to therapy or disease progression. In contrast, resolution of bone deformities is not to be expected despite successful treatment.

Prognosis is generally good if the underlying disease is curable. This applies both to rickets and to adult OM; with regards to the former, bone deformations may be permanent if therapy is initiated in a delayed manner or not at all. In these cases, rickets can be associated with significant morbidity. In adult OM, skeletal deformities are usually not an issue. However, pathological fractures are, and especially in post-menopausal women, osteoporosis is not a rare comorbidity. Such a condition may considerably complicate the healing process.

Bone mineralization is an ongoing process and both bone resorption (and subsequent release of minerals into circulation) as well as deposition of hydroxyapatite take place throughout life. These processes are regulated by a complex network of mediators, with vitamin D, parathyroid hormone (PTH) and calcitonin playing important roles. OM may be considered the result of a disturbance of those regulatory mechanisms, and may either be provoked by lack of resources or deficits in resource management. In detail, the following conditions may trigger OM:

• Vitamin D deficiency is the most frequent cause of OM. In fact, large parts of the adult population show certain degrees of vitamin D deficiency [1]. This vitamin may be endogenously synthesized, starting from cholesterol that is converted into cholecalciferol in the skin upon exposure to UV-light; further metabolization in the liver yielding 25-hydroxycholecalciferol (pre-vitamin D); and a final step that takes place in the kidneys and produces 1,25-dihydroxycholecalciferol (vitamin D). In case of insufficient exposure to sunlight, vitamin D has to be provided with the diet.
• Consequently, a combination of reduced exposure to sunlight, hepatic or renal disorders and inadequate dietary supply may cause vitamin D deficiency and secondary OM. With regards to the latter, there may be an absolute deficiency of vitamin D in the diet, but malabsorption of vitamin D is more common. Patients suffering from celiac disease have a particularly high risk of OM [2]. Bariatric surgery and gastrectomy realized for other reasons also predispose for vitamin D deficiency and OM. Of note, gastrointestinal disorders may also interfere with calcium absorption and thus contribute to decreases in bone density.
• Because conversion of pre-vitamin D into vitamin D depends on renal function, chronic kidney diseases may also lead to OM. The term chronic kidney disease and mineral bone disorder is sometimes used to refer to any renal disease that causes skeletal alterations. End-stage renal disease, for instance, is associated with histologic anomalies of osseous tissue in virtually all cases, but clinical manifestation of OM is rare [3].
• Renal disease related to an excess excretion of phosphorus may cause hypophosphatemia and secondary OM.
• Drug-induced OM is a possible side effect of therapy with cytochrome P450-inducing compounds [4].
• OM may be a symptom of Fanconi syndrome or osteodystrophia deformans (Paget disease).

Deposition and resorption of minerals in or from osseous tissue is a permanent, physiological process. Thus, disturbances of the equilibrium between both may affect people of any age. However, bone turnover is much more pronounced in children, whose skeleton constantly has to adapt to growth and changes of force distribution. Consequently, OM is generally more severe in pediatric patients. In fact, owing to the importance of that condition for the child's development, this disease has its proper name and is called rickets. OM is thus an umbrella term for rickets and adult OM, but is more commonly used to describe the latter.

Several epidemiological studies have been conducted to ascertain vitamin D deficiency, the most common cause of OM. It has been estimated that more than half of the population aged 60 years and older is vitamin D deficient [5], but this disease is also highly prevalent among children [6]. For the Western world, incidence of rickets in children aged up to three years has been reported to be approximately 6:100.000 [7]. Less reliable data are available for the adult population, presumably because OM is rarely diagnosed before symptoms manifest.

In OM, mineralization of osseous tissues is pathologically reduced. In order to understand how bone mineralization can be disturbed, it is essential to understand which physiological events eventually lead to deposition of hydroxyapatite in the organic matrix surrounding osteoblasts and osteocytes.

Hydroxyapatite is the main component of the inorganic bone matrix and mainly consists of calcium and phosphorus. Thus, an adequate supply of both minerals is essential for bone mineralization. Furthermore, the ratio of calcium and phosphorus significantly affects the availability of either electrolyte. In detail, low calcium:phosphorus levels, i.e., dietary restriction of phosphorus supply, have been shown to exacerbate demineralization.

Calcium and phosphorus have to be absorbed in the gastrointestinal tract and excessive renal excretion has to be prevented by reabsorption. On the other hand, appropriate measures need to be taken to avoid an overload with those electrolytes. Accordingly, regulation of serum levels of calcium and phosphorus depend on a variety of factors:

• Vitamin D stimulates intestinal absorption of calcium and enhances renal reabsorption of both electrolytes.
• PTH acts similarly, but favors renal excretion of phosphorus. Additionally, it provokes an increased release of bone-bound minerals into circulation. In sum, PTH aims to increase serum levels of calcium.
• Calcitonin counteracts those effects mediated by PTH. It inhibits intestinal calcium absorption, stimulates deposition of calcium and phosphorus in osseous tissue, and enhances renal excretion of calcium. Thus, it contributes to the reduction of serum levels of calcium.

Consequently, any pathological condition that results in vitamin D deficiency, hyperparathyroidism, or - at least theoretically - lack of calcitonin, may induce OM. In practice, the relative importance of the three aforementioned disorders decreases in the order stated.

As has been described above, vitamin D deficiency is the main cause of OM. However, PTH levels are not independent of serum concentrations of vitamin D. In fact, low levels of vitamin D stimulate PTH release. Thus, an individual who suffers from vitamin D deficiency may eventually develop secondary hyperparathyroidism [8].

Patients should be advised about maintaining a healthy, balanced diet. While nutritional deficiencies may be detrimental, excess supplementation of certain nutrients may have similar effects. Indeed, vitamin D is lipophilic and an overdose may have fatal consequences [10]. Dietary supplementation of vitamin D should not exceed 600 international units (IU) per day in patients aged 1 to 70 years. This also applies for pregnant and lactating women. Young infants may be prescribed 400 IU per day; people who are older than 70 years may ingest 800 IU daily. If at all possible, serum levels of vitamin D should be maintained in the range of 30 to 60 ng/ml.

Lack of exposure to sunlight and use of sunblock even though solar irradiation is low impair endogenous synthesis of vitamin D. Covering of the whole body, as frequently seen in Muslim women, has repeatedly been shown to increase the risk for bone disorders like OM.

Osteomalacia (OM) is a metabolic bone disease characterized by inadequate mineralization of osseous tissue. Function of osteoblasts, osteocytes and osteoclasts as well as the composition of the organic bone matrix is unaltered. In contrast, imbalances between bone formation and bone resorption account for the different entity osteoporosis.

Although OM may be diagnosed in patients pertaining to all age groups, it is not a congenital condition in the narrow sense of the word. It may be present in children, and is effectively known as rickets in such cases, but as per definition, it is an acquired disease. OM may, however, manifest as a complication of hereditary disorders.

The most common cause of OM is vitamin D deficiency, which, in turn, may result from insufficient dietary supply, malabsorption and disturbances of endogenous vitamin D synthesis. Furthermore, disturbances of calcium and phosphorus homeostasis may provoke OM.

Chronic pain, muscle weakness and pathological fractures are the most common signs of OM, and diagnosis is often delayed until such symptoms manifest. Identification of the underlying disorder is of utmost importance to treat the disease. The outcome largely depends on the primary disorder and the extent of bone deformations, if present.

Osteomalacia (OM) literally means "soft bones" and is a metabolic disorder that renders the skeleton less resistant, predisposes for bone pain and fractures. It is caused by disturbances in the bone mineralization.

The most common trigger of OM is vitamin D deficiency. Vitamin D plays an important role in maintaining calcium homeostasis and if vitamin D levels are below certain thresholds, the intestinal absorption of calcium is considerably reduced. If calcium is not provided, bones cannot be mineralized. Other causes of OM include lack of exposure to sunlight, disorders of the parathyroid glands and the kidneys.

Affected individuals often claim bone pain and muscle weakness, or report to have difficulties to rise from a sitting or prone position, or to climb stairs. Their susceptibility to fractures is increased and in fact, OM may not be diagnosed until a patient presents with a fractured bone.

Therapy consists in treating the underlying disease. Thus, in most cases, dietary supplementation of vitamin D, possible also of phosphate and calcium, may be recommended. However, overdosage may have detrimental effects. Thus, all patients should talk to their treating physicians about the necessary dose of nutrients in their particular case.

1. Haq A, Svobodova J, Imran S, Stanford C, Razzaque MS. Vitamin D deficiency: A single centre analysis of patients from 136 countries. J Steroid Biochem Mol Biol. 2016.
2. Albany C, Servetnyk Z. Disabling osteomalacia and myopathy as the only presenting features of celiac disease: a case report. Cases J. 2009; 2(1):20.
3. Santoro D, Satta E, Messina S, Costantino G, Savica V, Bellinghieri G. Pain in end-stage renal disease: a frequent and neglected clinical problem. Clin Nephrol. 2013; 79 Suppl 1:S2-11.
4. Wang Z, Lin YS, Dickmann LJ, et al. Enhancement of hepatic 4-hydroxylation of 25-hydroxyvitamin D3 through CYP3A4 induction in vitro and in vivo: implications for drug-induced osteomalacia. J Bone Miner Res. 2013; 28(5):1101-1116.
5. Souberbielle JC, Massart C, Brailly-Tabard S, Cavalier E, Chanson P. Prevalence and determinants of vitamin D deficiency in healthy French adults: the VARIETE study. Endocrine. 2016.
6. Turer CB, Lin H, Flores G. Prevalence of vitamin D deficiency among overweight and obese US children. Pediatrics. 2013; 131(1):e152-161.
7. Beck-Nielsen SS, Brock-Jacobsen B, Gram J, Brixen K, Jensen TK. Incidence and prevalence of nutritional and hereditary rickets in southern Denmark. Eur J Endocrinol. 2009; 160(3):491-497.
8. Erkal MZ, Wilde J, Bilgin Y, et al. High prevalence of vitamin D deficiency, secondary hyperparathyroidism and generalized bone pain in Turkish immigrants in Germany: identification of risk factors. Osteoporos Int. 2006; 17(8):1133-1140.
9. Dedeoglu M, Garip Y, Bodur H. Osteomalacia in Crohn's disease. Arch Osteoporos. 2014; 9:177.
10. Rajakumar K, Reis EC, Holick MF. Dosing error with over-the-counter vitamin D supplement: a risk for vitamin D toxicity in infants. Clin Pediatr (Phila). 2013; 52(1):82-85.