Alzheimer’s disease and bone mineral density

Alzheimer’s disease patients are also at a higher risk for hip fractures than healthy controls. A meta-analysis indicated that the Odds Ratio for hip fractures in patients with Alzheimer’s disease is 1.80 compared to healthy controls. Low bone mineral density and increased loss rate of bone mineral density were associated with higher risk of Alzheimer’s disease.

There are a lot of illnesses where there are both high homocysteine levels and decreased bone mineral densities, for example, Alzheimer’s diseases. High homocysteine levels and decreased bone mineral densities in range of illnesses can be tied together by dysregulations of the transsulfuration pathway in such illnesses.

Bipolar disorder and bone mineral density

There are decreases in bone mineral density in drug naive individuals with bipolar disorder compared to age- and gender-matched healthy controls. Individuals with bipolar I disorder have have high homocysteine levels. High homocysteine levels in individuals with bipolar disorder point to the transsulfuration pathway being dysregulated. Via the transsulfuration pathway L-cysteine is synthesized from homocysteine. L-taurine is synthesized from L-cysteine.

Taurine is required for calcium homeostasis. Taurine, also, is conjugated to various bile acids. Bile acids are are required for absorption of fat-soluble vitamins. Vitamin D and vitamin K are fat-soluble vitamins. Individuals with bipolar disorder are 4.7 times more likely to be vitamin D deficient than individuals amongst the general population of the Netherlands, however, deficient levels of vitamin D are not specific to bipolar disorder but are also present in individuals with schizophrenia. The taurine transporter is present in osteoblasts. Osteoblasts synthesize bone.

With taurine metabolism dysregulated calcium homeostasis is dysregulated and absorption of vitamin D and vitamin K is decreased. Decreases in bone mineral density in bipolar disorder could be due to dysregulation of the transsulfuration pathway which dysregulates calcium homeostasis and vitamin D and vitamin K absorption resulting in low bone mineral density.

Correction of osteomalicias can increase bone mineral density

There can be very large increases in bone mineral densities upon osteomalicias being corrected.

Long-term bone mineral density changes after surgical cure of patients with tumor-induced osteomalicia

L Colangelo , J Pepe, L Nieddu, C Sonato, A Scillitani, D Diacinti, M Angelozzi , C Cipriani, S Minisola

Abstract

Introduction: No systematic data are available regarding long-term bone mineral density (BMD) changes after surgical cure of patients with tumor-induced osteomalacia.

Methods: From October 2001 through April 2018, we studied 10 consecutive patients (mean age ± SD, 45.5 ± 13.8 years; 5 males and 5 females) with tumor-induced osteomalacia. We evaluated BMD when initially presented at our Center and after surgical removal of the tumor.

Results: Basal BMD and corresponding Z-score values (mean values ± SD) measured by DXA were as follows: L1-L4 = 0.692 ± 0.15 g/cm2, Z-score = – 2.80 ± 1.60; femur neck 0.447 ± 0.10 g/cm2, Z-score = – 2.66 ± 0.93; total femur = 0.450 ± 0.08 g/cm2, Z-score = -3.04 ± 0.85). Furthermore, Trabecular Bone Score (TBS) was evaluated in three patients (basal values, 0.990 ± 0.32). Seven patients were intermittently followed after surgical excision of the tumor while supplemented with cholecalciferol and calcium salts; the remaining three were lost to follow-up. There was a striking increase of BMD values that peaked at 26.7 ± 6.50 months: L1-L4 = 1.289 ± 0.247 g/cm2, p < 0.001, Z-score + 1.75 ± 1.42; femur neck = 0.890 ± 0.235 g/cm2, p = 0.028, Z-score = + 0.50 ± 1.40; total femur = 0.834 ± 0.150 g/cm2, p = 0.005, Z-score = – 0.74 ± 1.14. In patients with the greatest bone involvement at lumbar site, there was a striking increase of an average 1.5% (p < 0.01) in respect to baseline Z-score value for each additional month of observation during the first 2-3 years post-surgery. An improvement of trabecular microarchitecture was also documented (TBS, 1.255 ± 0.16).

Conclusion: This is the first case series documenting an impressive increase of BMD at both lumbar and femoral sites, together with an improvement of trabecular microarchitecture as documented by TBS. This is the consequence of huge mineralization of the large amount of osteoid tissue after resolution of the disease.

Bone mineral density and osteomalicias

Low bone mineral density with resulting osteoporosis is very frequently associated with osteomalicias though not always.

Bone mineral density in patients with osteomalicia: is it valuable?

Massoud Saghafi,  Azita Azarian, Kamila Hashemzadeh, Maryam Sahebari, Zahra Rezaieyazdi

Free PMC article

Abstract

Osteomalacia is a generalized bone disorder characterized by impairment of mineralization, leading to accumulation of unmineralized matrix or osteoid in the skeleton. The clinical features of osteomalacia include musculoskeletal vague pain and muscle weakness. In its mild and early stages, osteomalacia may be misdiagnosed with variety of musculoskeletal diseases including osteopenia and osteoporosis, and for early diagnosis high rate of suspicion of osteomalacia is necessary. Our purpose was to determine the amount of bone mineral density (BMD) in patients with osteomalacia and to evaluate the efficiency of bone densitometry in these patients. Diagnosis of our patients was based on history, physical, laboratory and radiological findings and in three patients with bone biopsy and histological approval. BMD (gm/cm(2)) at the lumbar vertebrae (L2-L4) and femoral neck were measured by dual X-ray absorptiometry in 20 patients with osteomalacia (16 females and 4 males, age range 20 to 60 years, mean 39 years) before treatment, comparing with 28 matched healthy individuals, and their T scores were evaluated according to WHO criteria for the diagnosis of osteopenia and osteoporosis. 14 patients with osteomalacia (70%) had BMD in amount of osteoporosis in the lumbar spine, and 12 patients with osteomalacia (60%) had BMD in amount of osteoporosis in their femoral neck. 50% of the patients had T≥ -3. We concluded that bone densitometry may detect osteoporosis in up to 70% of patients with osteomalacia. Middle aged individuals with significant osteoporosis should be evaluated for osteomalacia, beside other causes of secondary osteoporosis. Measurement of BMD in patients with osteomalacia is helpful for assessment of the severity of bone condition and following management.

Bone mineral density and major depression

Decreased bone mineral density is associated with major depression. There are also low vitamin D levels in individuals who are depressed. Ahedonia in major depression could be due to hidden osteomalicias. Taurine, vitamin D and vitamin K could treat hidden osteomalacias present in major depression. Supplements used to treat hidden osteomalicias, would not be effective for intense sadnesses that frequently occur with major depressions.

Bone mineral density and negative symptoms of schizophrenia

A meta-analysis points to bone mineral density being significantly decreased in individuals with schizophrenia compared to healthy controls. Bone mineral density in schizophrenia could be decreased in individuals with schizophrenia due to dysregulation of the transsulfuration pathway. Taurine is synthesized from L-cysteine which is synthesized via the transsulfuration pathway.

Taurine is required for intracellular calcium homeostasis. Bile acids are required for absorption of fat soluble vitamins. Vitamin D and vitamin K are fat soluble vitamins involved in bone formation. Various bile acids are synthesized from taurine. With deficiencies of taurine calcium homeostasis can be upset and there can also be deficiencies of vitamin D and vitamin K which could lead to low bone mineral density in schizophrenia.

Low bone mineral density in schizophrenia point to there being hidden osteomalicias in schizophrenia. With taurine deficiencies intracellular calcium homeostasis can be upset, though extracellular calcium levels could be normal, leading to a hidden osteomalicias.

Dysregulation of the transsulfuration pathway can result in epigenetic changes whereby there could be localized osteomalacias. Given osteomalacias due to taurine deficiencies develop in the back of the head negative symptoms of schizophrenia could develop due to compressions of cerebellums. There are a wide range of symptoms in schizophrenia so individuals with schizophrenia do not present as only having back of the head pains which makes correct diagnoses difficult though x-ray studies of backs of skulls in individuals with symptoms of schizophrenia could go a long ways in making correct diagnoses straightforward.

Negative symptoms of schizophrenia could be treated by supplementation with taurine, Vitamin K2 MK-7, which a kind of vitamin K that is highly absorbed, and vitamin D3. As negative symptoms of schizophrenia are due to hidden osteomalicias taurine, vitamin K2 MK-7 could take a long while to be completely effective. To treat the range of symptoms seen is schizophrenia due to dysregulations of the transsulfuration pathway supplements, beyond supplements that treat hidden osteomalicias, are required.