Once foods in the United States were fortified with vitamin D, rickets appeared to have been conquered, and many considered major health problems from vitamin D deficiency resolved. But vitamin D deficiency is common. This review considers the role of vitamin D in skeletal and nonskeletal health and suggests strategies for the prevention and treatment of vitamin D deficiency.

Vitamin D Deficiency

Objective: The objective was to provide guidelines to clinicians for the evaluation, treatment, and prevention of vitamin D deficiency with an emphasis on the care of patients who are at risk for deficiency. Participants: The Task Force was composed of a Chair, six additional experts, and a methodologist. The Task Force received no corporate funding or remuneration. Consensus Process: Consensus was guided by systematic reviews of evidence and discussions during several conference calls and e-mail communications. The draft prepared by the Task Force was reviewed successively by The Endocrine Society's Clinical Guidelines Subcommittee, Clinical Affairs Core Committee, and cosponsoring associations, and it was posted on The Endocrine Society web site for member review. At each stage of review, the Task Force received written comments and incorporated needed changes. Conclusions: Considering that vitamin D deficiency is very common in all age groups and that few foods contain vitamin D, the Task Force recomme...

/pdf/evaluation-treatment-and-prevention-of-vitamin-d-deficiency-4wt9apc7iy.pdf

Evaluation, Treatment, and Prevention of Vitamin D Deficiency: an Endocrine Society Clinical Practice Guideline

OBJECTIVE\nThe objective was to provide guidelines to clinicians for the evaluation, treatment, and prevention of vitamin D deficiency with an emphasis on the care of patients who are at risk for deficiency.\n\n\nPARTICIPANTS\nThe Task Force was composed of a Chair, six additional experts, and a methodologist. The Task Force received no corporate funding or remuneration.\n\n\nCONSENSUS PROCESS\nConsensus was guided by systematic reviews of evidence and discussions during several conference calls and e-mail communications. The draft prepared by the Task Force was reviewed successively by The Endocrine Society's Clinical Guidelines Subcommittee, Clinical Affairs Core Committee, and cosponsoring associations, and it was posted on The Endocrine Society web site for member review. At each stage of review, the Task Force received written comments and incorporated needed changes.\n\n\nCONCLUSIONS\nConsidering that vitamin D deficiency is very common in all age groups and that few foods contain vitamin D, the Task Force recommended supplementation at suggested daily intake and tolerable upper limit levels, depending on age and clinical circumstances. The Task Force also suggested the measurement of serum 25-hydroxyvitamin D level by a reliable assay as the initial diagnostic test in patients at risk for deficiency. Treatment with either vitamin D(2) or vitamin D(3) was recommended for deficient patients. At the present time, there is not sufficient evidence to recommend screening individuals who are not at risk for deficiency or to prescribe vitamin D to attain the noncalcemic benefit for cardiovascular protection.

Evaluation, treatment, and prevention of vitamin D deficiency: An endocrine society clinical practice guideline (Journal of Clinical Endocrinology and Metabolism (2011) 96, (1911-1930))

As people get older, they may fall more often for a variety of reasons including problems with balance, poor vision, and dementia. Up to 30% may fall in a year. Although one in five falls may require medical attention, less than one in 10 results in a fracture.
This review looked at the healthcare literature to establish which fall prevention interventions are effective for older people living in the community, and included 159 randomised controlled trials with 79,193 participants.  
Group and home-based exercise programmes, usually containing some balance and strength training exercises, effectively reduced falls, as did Tai Chi. Overall, exercise programmes aimed at reducing falls appear to reduce fractures.
Multifactorial interventions assess an individual's risk of falling, and then carry out treatment or arrange referrals to reduce the identified risks. Overall, current evidence shows that this type of intervention reduces the number of falls in older people living in the community but not the number of people falling during follow-up. These are complex interventions, and their effectiveness may be dependent on factors yet to be determined.  
Interventions to improve home safety appear to be effective, especially in people at higher risk of falling and when carried out by occupational therapists. An anti-slip shoe device worn in icy conditions can also reduce falls.
Taking vitamin D supplements does not appear to reduce falls in most community-dwelling older people, but may do so in those who have lower vitamin D levels in the blood before treatment.  
Some medications increase the risk of falling. Three trials in this review failed to reduce the number of falls by reviewing and adjusting medications. A fourth trial involving family physicians and their patients in medication review was effective in reducing falls. Gradual withdrawal of a particular type of drug for improving sleep, reducing anxiety, and treating depression (psychotropic medication) has been shown to reduce falls.
Cataract surgery reduces falls in women having the operation on the first affected eye. Insertion of a pacemaker can reduce falls in people with frequent falls associated with carotid sinus hypersensitivity, a condition which causes sudden changes in heart rate and blood pressure.
In people with disabling foot pain, the addition of footwear assessment, customised insoles, and foot and ankle exercises to regular podiatry reduced the number of falls but not the number of people falling.
The evidence relating to the provision of educational materials alone for preventing falls is inconclusive.

Interventions for preventing falls in older people living in the community

ContextRaloxifene hydrochloride, a selective estrogen receptor modulator, prevents
bone loss in postmenopausal women, but whether it reduces fracture risk in
these women is not known.ObjectiveTo determine the effect of raloxifene therapy on risk of vertebral and
nonvertebral fractures.DesignThe Multiple Outcomes of Raloxifene Evaluation (MORE) study, a multicenter,
randomized, blinded, placebo-controlled trial.Setting and ParticipantsA total of 7705 women aged 31 to 80 years in 25 countries who had been
postmenopausal for at least 2 years and who met World Health Organization
criteria for having osteoporosis. The study began in 1994 and had up to 36
months of follow-up for primary efficacy measurements and nonserious adverse
events and up to 40 months of follow-up for serious adverse events.InterventionsParticipants were randomized to 60 mg/d or 120 mg/d of raloxifene or
to identically appearing placebo pills; in addition, all women received supplemental
calcium and cholecalciferol.Main Outcome MeasuresIncident vertebral fracture was determined radiographically at baseline
and at scheduled 24- and 36-month visits. Nonvertebral fracture was ascertained
by interview at 6-month-interim visits. Bone mineral density was determined
annually by dual-energy x-ray absorptiometry.ResultsAt 36 months of the evaluable radiographs in 6828 women, 503 (7.4%)
had at least 1 new vertebral fracture, including 10.1% of women receiving
placebo, 6.6% of those receiving 60 mg/d of raloxifene, and 5.4% of those
receiving 120 mg/d of raloxifene. Risk of vertebral fracture was reduced in
both study groups receiving raloxifene (for 60-mg/d group: relative risk [RR],
0.7; 95% confidence interval [CI], 0.5-0.8; for 120-mg/d group: RR, 0.5; 95%
CI, 0.4-0.7). Frequency of vertebral fracture was reduced both in women who
did and did not have prevalent fracture. Risk of nonvertebral fracture for
raloxifene vs placebo did not differ significantly (RR, 0.9; 95% CI, 0.8-1.1
for both raloxifene groups combined). Compared with placebo, raloxifene increased
bone mineral density in the femoral neck by 2.1% (60 mg) and 2.4% (120 mg)
and in the spine by 2.6% (60 mg) and 2.7% (120 mg) P<0.001
for all comparisons). Women receiving raloxifene had increased risk of venous
thromboembolus vs placebo (RR, 3.1; 95% CI, 1.5-6.2). Raloxifene did not cause
vaginal bleeding or breast pain and was associated with a lower incidence
of breast cancer.ConclusionsIn postmenopausal women with osteoporosis, raloxifene increases bone
mineral density in the spine and femoral neck and reduces risk of vertebral
fracture.

https://jamanetwork.com/journals/jama/articlepdf/191242/JOC90496.pdf

Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial

Histomorphometric analysis of undecalcified sections was performed in transiliac biopsy cores taken from 29 patients (16 men, 13 women, aged 51 +/- 17 years) suffering from skeletal fluorosis due to chronic exposure to fluoride. The origin of the exposure, known in 20 patients, was either by water (endemic or sporadic), or industrial, or in a few cases iatrogenic. Measured on calcified bone using a specific ion electrode, bone fluoride content was significantly high in each specimen (mean +/- SD: 0.79 +/- 0.36% of bone ash) as compared to control values (less than 0.10%). The radiologically evident osteosclerosis observed in each patient was confirmed by the significant increase of cancellous bone volume (40.1 +/- 11.2 vs. 19.0 +/- 2.8% in controls, p less than 0.0001). There were significant increases in cortical width (1292 +/- 395 vs. 934 +/- 173 microns, p less than 0.0001) and porosity (14.4 +/- 6.4 vs. 6.5 +/- 1.7%, p less than 0.002), but without reduction of cortical bone mass. Osteoid parameters were significantly increased in fluorotic patients. The increase in cancellous osteoid perimeter was almost threefold greater than that noted in cancellous eroded perimeter. The fluorotic group had a greater number of osteoblasts than controls, with a very high proportion of flat osteoblasts. In 15 patients doubly labeled with tetracycline, the mineral apposition rate was significantly decreased, while mineralization lag time significantly increased. Bone formation rate and adjusted apposition rate were significantly decreased in skeletal fluorosis. Cancellous wall width was normal in fluorosis but the formation period and active formation period were significantly increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Skeletal fluorosis: Histomorphometric findings

Osteocalcin, also called bone gla-protein, is a bone matrix protein synthetized specifically by osteoblasts. It circulates in blood where it can be assayed by the radioimmune method. We measured osteocalcin serum levels in 169 adult controls and 161 patients with different disseminated or localized bone diseases. The normal concentration of 6.2 +/- 0.2 ng/ml increases significantly with age. Serum osteocalcin levels are considerably increased in renal osteodystrophy (114 +/- 23 ng/ml) and to a lesser degree in primary hyperparathyroidism (15.9 +/- 2.8 ng/ml) and Paget's disease (11.4 +/- 0.9 ng/ml), all diseases characterized by increased bone turnover. High levels are also encountered in osteomalacia (9.7 +/- 0.9 ng/ml). Conversely, serum osteocalcin levels are significantly decreased in patients under long-term corticosteroid therapy (4.3 +/- 0.5 ng/ml); they remain normal in patients with bone myeloma and bone metastases under treatment. Finally, osteocalcin is normal in patients with osteoporosis, but its level reflects that of bone turnover as evaluated by iliac bone biopsy. The circulating osteocalcin therefore is the first specific and sensitive marker for bone turnover. Serum osteocalcin measurements make it possible to evaluate the osteoblastic bone formation without biopsy and should provide information on the effectiveness of drugs acting on the bone-forming process.

[Osteocalcin (or bone gla-protein), a new biological marker for studying bone pathology].

1. The histological effects of deferoxamine therapy were assessed on transiliac bone biopsies taken after double tetracycline labelling from 16 uraemic patients undergoing chronic haemodialysis, all having aluminium deposits in bone. Eight patients had osteomalacia, five had an ‘aplastic’ bone lesion and three a high bone turnover with a marked increase in osteoid volume. 2. Deferoxamine was administered intravenously once a week at doses ranging from 1 to 6 g for a mean duration of 7.6 ± 3.3 (sd) months. 3. Deferoxamine therapy was associated with significant reductions in stainable aluminium deposits, osteoid volume, osteoid surfaces and thickness index of osteoid seams. The osteoblastic osteoid surfaces as well as the bone formation rates also increased significantly. 4. A rise in resorption parameters and in serum parathyroid hormone levels was observed in patients with osteomalacia. The percentage reductions in stainable aluminium and in osteoid volume were correlated with the degree of hyperparathyroidism. 5. These data show that deferoxamine therapy reduces stainable bone aluminium and improves bone mineralization in low turnover osteomalacia and that the presence of hyperparathyroidism is associated with an increased response to deferoxamine therapy.

Deferoxamine-induced bone changes in haemodialysis patients: a histomorphometric study.

Ossein-hydroxyapatite compound (OHC) is a protein-mineral complex derived from bovine bone. Its effects on bone remodeling were studied in old ewes which have seasonal variations in bone remodeling. Seven animals received 200 mg OHC/kg b.w./day for 90 days from July to September. The control group consisted of 7 untreated animals followed for the same period of time. OHC was administered through a fistula into the fourth stomach. A significant decrease of bone histomorphometric parameter values was noted in controls at the end of the experiment, due to seasonal variations: the cancellous eroded perimeter decreased by 45%, the osteoblastic perimeter by 60% and the bone formation rate at the cell level by 20%. In contrast, in the treated-group, these parameters tended to increase or did not change. In conclusion, counteracting the significant seasonal reduction of bone remodeling in ewes, OHC seems able to stimulate directly or indirectly bone metabolism, especially when osteoblast activity is reduced and may partly prevent the seasonal reduction of bone turnover.

Marie-Claire Chapuy

Papers

Skeletal fluorosis: Histomorphometric findings

[Osteocalcin (or bone gla-protein), a new biological marker for studying bone pathology].

Deferoxamine-induced bone changes in haemodialysis patients: a histomorphometric study.

Effects of ossein-hydroxyapatite compound on ewe bone remodeling: biochemical and histomorphometric study.

Increased vertebral bone density in heavy drinkers of mineral water rich in fluoride.